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Review

Aspergillus nidulans—Natural Metabolites Powerhouse: Structures, Biosynthesis, Bioactivities, and Biotechnological Potential

by
Kholoud F. Ghazawi
1,
Sarah A. Fatani
2,
Shaimaa G. A. Mohamed
3,
Gamal A. Mohamed
4 and
Sabrin R. M. Ibrahim
5,6,*
1
Clinical Pharmacy Department, College of Pharmacy, Umm Al-Qura University, Makkah 24382, Saudi Arabia
2
Department of Clinical Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
3
Faculty of Dentistry, British University, El Sherouk City, Suez Desert Road, Cairo 11837, Egypt
4
Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
5
Preparatory Year Program, Department of Chemistry, Batterjee Medical College, Jeddah 21442, Saudi Arabia
6
Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
*
Author to whom correspondence should be addressed.
Fermentation 2023, 9(4), 325; https://doi.org/10.3390/fermentation9040325
Submission received: 23 February 2023 / Revised: 13 March 2023 / Accepted: 23 March 2023 / Published: 25 March 2023
(This article belongs to the Special Issue New Research on Fungal Secondary Metabolites)
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Versions Notes

Abstract

:
Nowadays, finding out new natural scaffolds of microbial origin increases at a higher rate than in the past decades and represents an auspicious route for reinvigorating the pool of compounds entering pharmaceutical industries. Fungi serve as a depository of fascinating, structurally unique metabolites with considerable therapeutic significance. Aspergillus genus represents one of the most prolific genera of filamentous fungi. Aspergillus nidulans Winter G. is a well-known and plentiful source of bioactive metabolites with abundant structural diversity, including terpenoids, benzophenones, sterols, alkaloids, xanthones, and polyketides, many of which display various bioactivities, such as cytotoxicity, antioxidant, anti-inflammatory, antiviral, and antimicrobial activities. The current work is targeted to survey the reported literature on A. nidulans, particularly its metabolites, biosynthesis, and bioactivities, in addition to recent reports on its biotechnological potential. From 1953 till November 2022, relying on the stated data, 206 metabolites were listed, with more than 100 references.

1. Introduction

With the increase in the burden of non-communicable diseases, as well as the growing antimicrobial-resistant infections, the need for new agents that can supply amended therapeutic outcomes has taken on the utmost primacy. Therefore, the investigation of microbes is one of the auspicious ways of finding out lead molecules for drug discovery. Fungi are among the microbes that possess enormous negative and positive influences on human lives [1,2]. They serve as a depository of biometabolites that represent the backbone of different available pharmaceuticals. Moreover, fascinating, structurally unique metabolites, with considerable therapeutic significance as antibiotics as well as anticancer, antidiabetic, antiviral, and immuno-suppressive agents, have been reported in these untapped micro-organisms [3,4,5,6,7,8,9,10,11,12,13]. In addition, they have proved to be superbly efficient decomposers and have developed the capacity to feed on and break down polymeric substances and organic matter by secreting various enzymes, providing sustainable solutions for diverse industries and markets [7,14,15].
Additionally, fungal biotechnology may assist human society’s transition from a petroleum-dependent to a bio-based circular economy. Moreover, they are able to sustainably produce feed, food, chemicals, textiles, fuels, and more [1,2]. On the other hand, they also manufacture toxins that spoil different foods, and they predominantly infect immuno-compromised patients, which drives up public health costs [1,2].
The Aspergillus genus (Trichocomaceae, class Discellaceae), with more than 400 species, represents one of the most prolific genera of filamentous fungi [16]. Aspergillus is an anamorphic (asexual) genus; some of its species have teleomorphs (sexual states), such as A. nidulans, which in its sexual state is called Emericella nidulans [17]. Its species are encountered in outdoor and indoor environments and have relevant medical, food, and industrial applications [16,17,18,19]. Additionally, this genus is renowned for its biosynthesizing of diverse classes of metabolites with myriad bioactivities [5,16,20,21]. Moreover, some of its species have potential biotechnological and industrial applications [16,22]. On the other hand, some cause diverse illnesses to animals and humans [23,24].
Among this species, Aspergillus nidulans Winter G was reported to cause cerebral aspergillosis and is a common pathogen in patients with chronic granulomatous disease [25,26,27]. A. nidulans is well known for its plentiful sources of bioactive metabolites with abundant structural diversity, including terpenoids, alkaloids, polyketides, many of which display various biological activities, such as antioxidant, antialgal, anti-mycobacterial, antiviral, plant growth promoting, cytotoxicity, anti-inflammatory, and antimicrobial activities. In addition, A. nidulans has the potential to secrete various enzymes: laccase, β-glucosidase, keratinase, cellulase, xylanase, lipase, β-galactosidase, cutinase, protease, tannase, and aryl alcohol oxidase [28]. It is noteworthy that the A. nidulans genetic model has been extensively studied regarding cellular development, metabolism, and gene regulation, contributing to an understanding of eukaryotic cell biology and molecular processes, where the capabilities of its genetic manipulation and combining of genetic traits via sexual crossing are important for its marked function as a genetic model [29].
The prime aim of this work is to focus on the stated research on A. nidulans collected from various sources, particularly the structures, biosynthesis, and bioactivities of its metabolites. Moreover, recent reports on its biotechnological relevance, as well as nanoparticle synthesis, have been reviewed. Reported studies from 1953 to November 2022 are presented. The molecular formulae and weights, chemical classes, hosts, location, and bioactivities for its metabolites are listed. The structures of these metabolites according to their chemical classes are summarized. The present work could provide a guide for future expected research exploring the untapped potential of A. nidulans as one of the prosperous producers of bio-metabolites.

2. Methodology

2.1. Data Collection

A survey of the literature was done using assorted databases and publishers: Scopus, PubMed, GoogleScholar, ScienceDirect, Wiley, Taylor & Francis, Bentham, Thieme, MDPI, and Springer. The search was carried out using “Aspergillus nidulans + compounds”, OR “Aspergillus nidulans + NMR”, OR “Aspergillus nidulans + biosynthesis”, OR “Aspergillus nidulans + Biological activity”, “Aspergillus nidulans + Biotechnology”, “Aspergillus nidulans + Enzymes”, OR “Aspergillus nidulans + nanoparticles” as keywords. All chemical structures were drawn utilizing ChemDraw.

2.2. Data Selection

The criteria for the reported data selection included in this review were: (1) studies that reported A. nidulans’ metabolites, including their structures, biosynthesis, and bioactivities, as well as biotechnological importance and nanoparticle synthesis using A. nidulans; (2) all the reported data published in peer-reviewed journals (e.g., articles, reviews, abstracts); and (3) reviews and book chapters. Included studies were assessed through reading of titles, abstracts, and full texts. For non-English articles, the data were extracted from the English abstracts. In this work, published data covering the period from 1953 to November 2022 have been included. In the current work, 103 references have been cited, including various articles and books.

3. Metabolites of Aspergillus nidulans and their Bioactivities

Several studies reported the separation and characterization of assorted classes of metabolites, employing various chromatographic and spectral tools that are surveyed herein, along with their estimated bioactivities and postulated biosynthesis pathways. It was noted that among the diverse metabolites reported from this species, a limited number of them have been assessed for biological capacity (Table 1).

3.1. Benzophenones

A. nidulans and its teleomorph Emericella nidulans are known to biosynthesize prenylated structurally related benzophenones [43,44,45]. Many investigations remarked upon the separation of arugosins, which are interesting fungal metabolites that involve the biosynthesis of structurally related polyketides (e.g., anthraquinones, anthrones, xanthones) (Table 2) [31,43,44,45,46].
The fungus E. nidulans var. acristata, isolated from a Mediterranean green alga, yielded two new benzophenones, arugosins G (10) and H (3), together with arugosins A (7) and B (8) that were separated from the EtOAc extract by Sephadex LH-20/HPLC (Figure 1). These metabolites featured prenyl moieties that are connected to the skeleton via an ether linkage. Compound 3 had antifungal and antialgal potential (IZDs 2 and 3 mm, respectively) vs. Mycotypha microspora and Chlorella fusca, respectively, whereas 7 and 8 (mixture) revealed antibacterial influence vs. Bacillus megaterium (IZD 4 mm) in the agar diffusion assay [43]. Additionally, 7 and 8 demonstrated modest antitumor effectiveness vs. individual cancer cell lines [43]. It is noteworthy that arugosins A (7) and B (8), dibenz[b,e]oxepin metabolites that were formerly reported from A. silvaticus, A. rugulosus, and A. variecolor, and arugosins C and F were obtained from Aspergillus spp. and Ascodesmis sphaerospora, respectively [43].
Arugosin H (3) was proposed as originating from chrysophanol (29, anthrone), which performs oxidative cleavage to produce the aldehyde group, which subsequently undergoes hydroxylation and C-prenylation (Scheme 1). Further, the aldehyde group is converted to a hemiacetal function to produce tricyclic and prenylated metabolites 7, 8, and 10 [43].

3.2. Xanthones and Quinones

Xanthones are dibenzo-γ-pyrone derivatives that differ in the substituents on the benzene rings, relying on modification reactions and biosynthetic origins. Fungal xanthones are polyketides created mainly from acetate units and commonly contain a CH3 group. It was reported that A. nidulans produces prenylated xanthones with varied structures.
Compounds 14, 16, and 18 are xanthones reported from green alga-derived E. nidulans var. acristata (Table 3). Among them, 18 had antifungal and antialgal capacity (IZDs 11 and 5 mm, respectively) vs. M. microspora and C. fusca. However, none of them exhibited immune-stimulatory potential against cytokine induction in PBMCs [43]. Compounds 14 and 18 were reported from A. nidulans and isolated from Red Sea brown alga, Turbinaria elatensis, using SiO2 and Sephadex LH-20 CC. They had mild inhibition capacity on HCV NS3/4A protease (IC50s 48.5 and 50.0 μg/mL, respectively), compared to HCV-12 (IC50 1.5 μg/mL) [47]. In 2018, isosecosterigmatocystin (15), a new xanthone, in addition to 18, was separated and identified from the EtOAc culture extract of A. nidulans MA-143 under 0.1% ethanol stress. Compound 15 was assigned as having 2′S/3′S based on X-ray analysis [30].
The cytotoxic capacity of 18 and 20 vs. NCI-H460, MCF-7, and HeLa cell lines in the SRB was assessed. Only 18 (IC50 50 μM/mL) possessed growth inhibition capacity vs. the MCF-7 cell, whereas 20 was inactive (IC50 > 100) [53] (Figure 2).
Also, the xanthones were proposed to be biosynthesized from 29, which is transformed by quinone ring oxidative cleavage into thiolester I. Its oxidoreductase-catalyzed reduction yields benzophenone alcohol (II). The alcohol (II) produces 1-hydroxy-6-methyl-8- hydroxymethylxanthone (III) via H2O elimination, and then hydroxylation via monooxygenase produces 1,7-dihydroxy-6-methyl-8-hydroxymethylxanthone (IV). The latter’s prenyltransferase-catalyzed prenylation results in 12, which is C-prenylated to form 14. Subsequent cyclization of 14 produces 16 and 17 (Scheme 2) [45].
Nidurufin (42), a new metabolite of which is hydroxyaverufin, and 39 were purified from the CHCl3:MeOH extract of A. nidulans G-106 using silica and formamide-impregnated cellulose powder and characterized by spectral and chemical methods (Figure 3) [51].
The aggregation of the microtubule-accompanied protein tau is substantial in various neurodegenerative illnesses, such as Alzheimer’s disease. Interestingly, 25 and 30 demonstrated potent tau aggregation inhibition potential, which was observed in a filter trap assay and by electron microscopy. In addition, 25 and 30 lessened tau aggregation without blocking tau stabilization of microtubules, like 23.
Together, these metabolites demonstrated potential as lead compounds for developing tau aggregation inhibitors in Alzheimer’s disease and neurodegenerative tauopathies [54]. Isoversicolorin C (36), a new anthraquinone derivative, and six related metabolites—34, 35, 39, 45, and 44—were purified and characterized from the EtOAC culture extract of mangrove-derived A. nidulans MA-143 under ethanol 0.1% stress (Figure 4). Their isolation and elucidation were accomplished by SiO2/RP-18/Sephadex LH-20 and NMR/ECD/X-ray. Compound 36 had potent antibacterial capacity vs. E. ictaluri and V. alginolyticus (MICs 4.0 and 1.0 μg/mL, respectively); however, 35 possessed capacity vs. M. luteus, E. coli, V. parahaemolyticus, V. alginolyticus, and E. ictaluri (MICs ranged from 1.0 to 8.0 μg/mL), which were comparable to chloramphenicol [30].

3.3. Depsidones and Biphenyl Ethers

Depsidones consist of two 2,4-dihydroxy-benzoic acid moieties, connecting via ester and ether bonds, resulting in 11H-dibenzo[b,e] [1,4] dioxepin-11-one core formation [59]. They originated from depsides’ direct-oxidative coupling of the A 2OH ring and the B 5′ carbon ring. These metabolites were found to have diversified potential: anti-malarial, herbicidal, anti-leishmanial, larvicidal, antifungal, cholinesterase and aromatase inhibitory, and antioxidant activity [59].
Compounds 48 and 49 were separated from the A. nidulans mycelia’s light petroleum ether extract by repeated crystallization from the EtOH and petroleum ether (Table 4). Compound 48 is a monomethyl ether that completely suppressed Mycobacterium tuberculosis growth for 4 weeks, as well as Microsporum audouini and Trichophyton tonsurans, and was inactive against bacteriophages [60].
The co-culture of A. nidulans and A. fumigatus enhanced the production of diphenyl ethers, 52–55, which were separated by SiO2 CC/HPLC and identified by NMR tools (Figure 5). These metabolites (52–55) possessed antibacterial potential against B. subtilis (MICs 6.3–100 μg/mL) compared to chloramphenicol, indicating that the hydroxylation enhanced the antibacterial effect of diphenyl ethers [32]. In addition, 56 revealed potent antimicrobial effectiveness (MICs 2–4 μg/mL) vs. E. ictarda, A. hydrophilia, E. tarda, and V. harveyi (aquatic pathogens) and C. gloeosporioides (pathogenic plant fungus), which could be further studied in terms of developing antimicrobial agents [31].

3.4. Alkaloids

3.4.1. Quinolone Alkaloids

Natural quinoline alkaloids are an abundant class of alkaloids that have been reported as having animal, plant, and microbial origins. Some investigations remarked upon the separation of quinoline alkaloids from A. nidulans.
A combined analytical and genomic approach and metabolic investigation of A. nidulans HKI 0410 under various culture conditions resulted in aspoquinolones A-D (61–64), which were separated utilizing SiO2/Sephadex LH-20/HPLC and assigned by NMR [62]. Compounds 61 and 62 are isomers with 3-methoxy-4,6-dihydroxy-4-(4′-methoxyphenyl)quinolinone and unusual 2,2,4-trimethyl-3-oxa-bicyclo[3.1.0]hexane moieties; however, 63 and 64 are diastereomers (ratio 2:1) sharing the same 3-methoxy-4,6-dihydroxy-4-(4′-methoxyphenyl)quinolinone skeleton as 61 and 62 (Figure 6; Table 5). Compounds 61 and 62 exhibited remarkable cytotoxic and antiproliferative capacity on L-929 (GI50 10.6/11.4 μg/mL) and K-562 (GI50 17.8/21.2 μg/mL) cell lines, respectively.
These metabolites were postulated as originating from cyclopenin (benzodiazepine, I) formed from anthranilic acid and tyrosine/or phenylalanine, which is biosynthesized by anthranilate synthase (Scheme 3). This enzyme catalyzed the conversion of chorismate to anthranilic acid for tryptophan biosynthesis [62].
From Annelida Whitmania pigra-associated A. nidulansi, aspoquinolones E (65) and F (66), new prenylated quinolinone alkaloids were purified utilizing SiO2/Sephadex LH-20/HPLC. Their configurations and structures were determined based on spectral and ECD analyses. They featured 3S/4S configuration, with an unusual 2,2,4-trimethyl-3oxa-bicyclo[3.1.0]hexane moiety. Their cytotoxic evaluation vs. A-549, HL-60, and MCF-7 revealed that 65 exhibited moderate cytotoxic capacity (IC50s 3.50, 29.15, and 24.5 μM, respectively) compared to cis-platin (IC50s 13.17, 3.22, and 22.96 μM, respectively). It is noteworthy that 65 and 66, with the same structure but different cyclopropyl ring configuration, were greatly varied in activity, suggesting that the cyclopropyl ring configuration influenced the activity [33].
In 2013, the separation of new 4-phenyl-3,4-dihydroquinolone derivatives, 67–72, along with known related analog 73, was reported from a Rhizophora stylosa-associated A. nidulans MA-143 extract by SiO2/RP-18/sephadex LH-20/HPLC. Their structures and absolute configuration were established by spectral, ECD, and X-ray analyses. Compounds 70–72 share with 67–69 the 4-phenyl-3,4-dihyroquinolone moiety but lack the terpenoid side chain, as in 67–69. Additionally, 67 was related to 73; however, 67 lacks the cyclohexane moiety in the terpenoid side chain of 73; instead, it features a terminal double bond and substituted tetrahydrofuran moiety. These metabolites did not have cytotoxic (vs. BEL-7402, MDA-MB-231, HL-60, and K562) or antibacterial (E. coli and S. aureus) potential in the MTT and well diffusion methods, respectively, while 68, 69, and 73 had a marked brine shrimp lethality (LD50 7.1, 4.5, and 5.5 μM, respectively) that was more powerful than colchicine (LD50 88.4 μΜ) [34].

3.4.2. Quinazolinone, Pyrazine, and Dioxopiperazine Alkaloids

Additionally, four new quinazolinone alkaloids, namely aniquinazolines A–D (74–77), were also purified from E. nidulans using SiO2/Sephadex LH-20/HPLC and elucidated by spectral analyses, and their absolute configurations were assigned based on acidic hydrolysate chiral HPLC, ECD, and X-ray analyses (Figure 7). Their configurations are 3R/14R/17R/18R/20S (74 and 76), 3R/14R/17R/18R (75), and 14R/17S/18S/20S (77). Compounds 74–77 had potent brine shrimp lethality (LD50s 1.27–4.95 μΜ) compared to colchicine (LD50 88.4 μΜ). Unfortunately, they did not have anticancer potential vs. MDA-MB-231, BEL-7402, K562, and HL-60 or antibacterial capacity vs. E. coli and S. aureus in the MTT and well diffusion assays, respectively [35].
Emestrin (82), a six-membered-ring dioxopiperazine with a disulfide bridge, is part of the epipoly-thio-dioxopiperazine family obtained from ascidian Aplidium longithorax-associated E. nidulans MFW39 and collected from Wakatobi Marine National Park, Indonesia utilizing SiO2 CC/HPLC (Table 6). It was found to have noticeable cytotoxic potential (IC50s ranged from 1.8 to 13.8 µg/mL) vs. C28, T47D, HeLa, and HepG2 but was weakly active against Vero cells (IC50 260.9 μg/mL). Emestrin (Conc. 1.0 μg/mL) caused G0/G1 arrest of the cell cycle, and also induced apoptosis (Conc. 1.0 and 3.0 μg/mL) of 83.6 and 92.6%, respectively, on T47D cells. This effect was linked to a disulphide bond and unique epithio-dioxopiperazine moiety [36]. Another epipolythiodioxopiperazine derivative, emestrin B (83), was separated from marine-derived E. nidulans using SiO2 CC/preparative TLC and was assessed for cytotoxic capacity in the MTT assay vs. the WiDr, HeLa, and T47D cancer cell lines. It had remarkable cytotoxic influence on IC50s 1.02, 1.56, and 0.16 μg/mL, respectively. This metabolite had apoptotic action against T47D cells (74.1%), compared to doxorubicin (74.8%) [37]. Compound 84, purified from the Nyctanthes arbor-tristis-inhabited fungus strain, had no cytotoxic effectiveness vs. the NCI-H460, MCF-7, and HeLa cell lines in the SRB [53]. Glulisine A (81), a new nitrogenous metabolite, was reported from 1% ethanol-stressed A. nidulans MA-143. It was assigned by NMR and X-ray analyses as being derived from leucine and glutamine [30].

3.4.3. Indole Derivatives

The indole alkaloid emindole DA (97), separated from green alga-associated fungus, possessed antitumor potential vs. 36 human tumor cell line panels (mean IC50s 5.5 µg/mL) in the propidium iodide fluorescence assay [43]. In an antimicrobial assay vs. various aquatic, plant, and human pathogens, terrequinone A (92) exhibited marked efficacy (MIC 2 μg/mL) vs. E. coli, V. alginolyticus, and C. gloeosporioides, compared to chloramphenicol and amphotericin B, suggesting the potency of 92 as a lead metabolite for antimicrobial agents [31]. Ergotryptamine (87) is an alkaloid produced by an engineered A. nidulans WFC that was designated using labeling, MS, and NMR tools. It differs from N-methyl-4-dimethylallyltryptophan (88) by the addition of the OH group, loss of the COOH group, and shifting of the double bond position [64] (Figure 8).

3.4.4. Isoindole Derivatives

The production of new isoindole alkaloids, aspernidine A (99) and B (100 X2), by A. nidulans AXB4A2 cultivated in malt medium at increased orbital shaking (200 rpm) and elevated temperature (37 °C) with p-aminobenzoate/uridine supplementation, was reported. These metabolites were separated via SiO2/Sephadex LH-20/HPLC and characterized by MS and NMR tools (Figure 9). Compounds 99 and 100 had moderate anti-proliferation potential with respect to L-929 and K-562 (GI50 35.8/34.3 μM for 99 and 39.5/39.5 μM for 100, respectively) and weak cytotoxicity with respect to HeLa (CC50 94.0 and 65.5 μM, respectively) [65] (Table 7).
It was reported that biosynthesis of 99 starts with orsellinaldehyde from PKS-PkfA, which undergoes hydroxylation, one phenolic OH methylation, and prenylation to produce 197. Subsequently, hydroxylation of 197 yields 198 [49]. It was hypothesized that 198 is oxidized to produce asperugin, and then it is transformed into aspernidine A (99) through a series of steps [49] (Scheme 4).
From the red alga Polysiphonia scopulorum var. villum-associated A. nidulans EN-330, two new indole diterpenes are produced: 19-hydroxypenitrem A (93) and 19-hydroxypenitrem E (94), which are chlorinated and dechlorinated indole diterpenoids, respectively, along with known congeners 95 and 96, which were purified from the EtOAc cultures and acetone extracts by SiO2/Sephadex LH-20/HPLC and characterized by NMR and CD analyses. These metabolites feature an indole skeleton produced from a tryptophan precursor (indole-3-glycerol-phosphate) and geranyl-geranyl diphosphate-derived cyclic diterpenoid framework. Penitrem A (95) belongs to a rare tremorgenic mycotoxins group that has a C-19 skeleton fused to C-2 and C-3 of the indole moiety. Compound 93 is like 95, but it has C19-oxygenated quaternary carbon instead of the methine in 95. Both 93 and 94 are 19S/22S/31R/32S configured. In the brine shrimp assay, 93–96 possessed potent cytotoxic effectiveness (LD50s 3.2, 4.6, 1.7, and 8.7 μM, respectively), in comparison to colchicine (LD50 10.7 μM), where 93 and 95 were more powerful than 94, indicating that the C-6 Cl-substitution boosted the activity, while the 19-OH group suppressed it (93 vs. 95) [38]. In the assay for antibacterial activity against aquatic- (E. tarda and V. anguillarum) and human-pathogens (E. coli and S. aureus), 93–95 demonstrated moderate antimicrobial potential vs. E. tarda, V. anguillarum, E. coli, and S. aureus (MICs ranged from 16 to 64 μg/mL) [38].
From Annelida Whitmania pigra-associated A. nidulansi, aspernidines F–H (102–104), new prenylated isoindolinone alkaloids were purified and characterized utilizing SiO2/Sephadex LH-20/HPLC and spectral/ECD analyses, respectively. They possess a C5-linked C15 side chain. Compounds 103 and 104 exhibited moderate cytotoxic capacity on A-549, HL-60, SMMC-7721, SW-480, and MCF-7 (IC50s ranged from 4.77 to 33.03 μM) compared to cis-platin (IC50 3.22–22.96 μM). It was observed that 104 exhibited powerful inhibitory capacity vs. SW-480 cells (IC50s 4.77 μM) compared to cis-platin (IC50s 18.01 μM) [33].
In 2016, novel meroterpenoids, emericellolides A–C (105–107) and emeriphenolicins E–G (108–110), with an isoindolone nucleus were separated from an A. nidulans HDN12.249 EtOAc broth extract isolated from Tamarix chinensis leaves that were obtained from Laizhou Bay using SiO2/RP-18/Sephadex LH-20/HPLC. Compounds 105–107 are characterized by an unparalleled macrolide skeleton consisting of an isoindolone moiety, an uncommon L-glutamate unit, and a sesquiterpene unit, while emeriphenolicins E–G (108–110) are rare isoindolone-based meroterpenoids with two farnesyl units linked to the isoindolone unit. These metabolites were structurally elucidated using NMR, MS, Mo2(AcO)4-induced ECD, chemical conversion, and Marfey’s method. In the SRB assay, only 108 exhibited selective potential vs. A549, HeLa, and HCT-116 (IC50s 12.04, 4.77, and 33.05 μM, respectively); however, the others were ineffective (IC50 > 50 μM) [39]. It was proposed that these metabolites were produced from asperugin A or B as an intermediate (Scheme 5). Further, farnesyl and L-glutamate units are formed through additional post-modifications, such as oxidation, methylation, and intra-molecular esterification [39].

3.4.5. Other Nitrogenous Compounds

Compound 111 was purified from cultured A. nidulans MeOH extract using alumina CC and crystallization from water. This compound had cytotoxic capacity vs. KB cells (endpoint value of 10–25 μ/mL and lethal endpoint of 50–100 μ/mL) [67], as well as inhibition of HCV NS3/4A protease (IC50 24.5 μg/mL), compared with HCV-12 (IC50 1.5 μg/mL), in addition to its potent cytotoxicity with inhibition zone difference of 100–200 mm vs. L1210, CCRF-CEM, colon 38, H-125, and HEP-G2 in the disc diffusion assay [47] (Figure 10).
The cerebroside, flavuside B (113), reported from orange peel-associated E. nidulans, had no antimalarial, antimicrobial, or antileishmanial capacities [68] (Table 8).

3.5. Peptides

Diverse strategies have evolved to take advantage of the biosynthetic stockpile of fungi. Various strategies are reported to better utilize the BGC (biosynthetic genes cluster) of this fungus.
The identification of aspercryptins (116–133), a new family of lipopeptides via prohibition of histone deacetylase (HDACi) in A. nidulans, was reported. They were discovered by NMR and MS/MS metabolite screening (Figure 11, Figure 12, Figure 13 and Figure 14). These metabolites are six-amino-acid peptides, having two non-canonical α-amino acids derived from saturated C12 and C8 fatty acids and a C-terminal alcohol [69] (Table 9). Hence, HDACi could be utilized for finding out new metabolites, even from fungal species that were intensively investigated.

3.6. Terpenoids and Sterols

Terpenoids and sterols are among the metabolites reported from E. nidulans that are derived from mevalonate via a key step of cyclization and elimination reaction, respectively.
The engineered A. nidulans biosynthesized 134, which was extracted using ASE (accelerated solvent extraction) and purified by HPLC (Table 10). In the DPPH assays, it had more powerful antioxidant potential than beta-carotene; however, it had no antimicrobial or anti-Leishmanial (50 µM) potential [71].
In 1983, β-amyrin was the first triterpenoid separated from A. nidulans [73]. From Whitmania pigra (Annelida, segmented worm)-associated A. nidulans, new sesterterpenoids, niduterpenoids A (136) and B (137), were reported that were purified from the EtOH culture extract by SiO2/Sephadex LH-20/HPLC (Figure 15). These metabolites were distinguished by a highly congested 5/5/5/5/3/5 hexacyclic skeleton without unsaturated functional groups, based on spectral and X-ray analyses [40]. They were assessed for their ERα (estrogen receptor α) inhibitory and cytotoxic potential vs. MCF-7 in the MTT assay. Compound 136 had no obvious cytotoxic potential, even at 80 μM, while it abolished the 17-estradiol-induced cell proliferation (IC50 11.42 μM) in a dose-based way. Molecular docking revealed that 136 and 137 fitted well with the ERα ligand-binding site and partially occupied the lasofoxifene (potent Er modulator) whole pocket. They formed key H-bonds with Arg346/Glu353/Met295 and a highly hydrophobic envelope with Leu298/Phe356/Phe377/Met294/Leu354. These findings indicated 136 was a potential ERα antagonist that required further studies [40].
These metabolites are the first reported sesterterpenes with a hexacyclic ring system having an uncommon cyclopropane moiety (Scheme 6). It was proposed that they were biosynthesized from GFPP through various cyclization and Wagner–Meerwein alkyl shift and hydride reactions, producing the X (key intermediate) with a hexacyclic 5/5/5/5/3/5 framework. Additional oxidation reactions result in 136 and 137 [40].
Compounds 138, 139, and 142 are meroterpenoids separated from a cold spring, deep-sea-sediment-associated strain that had no antimicrobial capacity vs. aquatic/human bacteria and pathogenic plant fungi [31].
The separation of new metabolites 145 and 148–150 was reported, in addition to 146, 151–154, and 156 from the EtOAc extract of the fungus A. nidulans, utilizing SiO2/Sephadex LH-20/HPLC and elucidated by spectral, ECD, and X-ray analyses (Figure 16).
These metabolites were assessed for cytotoxic potential in vitro vs. the PC12 cell line in the MTT assay. Only 145 possessed moderate potential (IC50 7.34 µM) compared to doxorubicin (IC50 5.71 µM) [41]. Compound 167, reported from the EtOAc broth extract of Emericella nidulans, was mildly active as an HCV inhibitor (IC50 47.0 μg/mL) relative to HCV-12 (IC50 1.5 μg/mL) [47] (Figure 17, Table 11).

3.7. Lactones and Furanones

A new metabolite, 172, was separated from the acetone culture extract of A. nidulans IFO6398 by SiO2 CC using benzene as eluent. It featured two mono-substituted phenyl and maleic anhydride moieties; this compound was assigned by spectral analyses. In the radish seedlings bioassay, 172 accelerated root elongation (Conc. 30 and 100 g/L, respectively), while it had no notable influence on the hypocotyl elongation at the same concentrations. Moreover, 172 boosted root elongation and prohibited hypocotyl growth (Conc. 100 mg/L) in the lettuce seedling bioassay [75]. Compound 179, separated from the A. nidulans IFO6398 acetone extract, boosted root elongation (Conc. 30 g/L) and showed no notable effect on lettuce seedling growth (Conc. 3, 10, 30, and 100 mg/L) in the radish and lettuce seedling bioassays, respectively [75] (Table 12).
Microperfuranone (173), purified and characterized from E. nidulans var. acristata, had no antimicrobial, cytotoxic, and immune-stimulating activity [43], while 173 and 174 had antimicrobial potential against aquatic, human, and plant pathogens (MICs ranged from 4 to 64 μg/mL), whereas 173 presented notable effectiveness vs. E. ictarda (MIC 4 μg/mL) compared to chloramphenicol (MIC 2 μg/mL) [31] (Figure 18).

3.8. Polyketides and Glycerides

A new polyketide, koninginin H (187), together with 184–186 and 193–196, was reported from E. nidulans isolated from an orange peel (Figure 19, Table 13). Compound 187 belongs to the koninginin class of metabolites that was encountered in the Trichoderma genus [68]. An antimicrobial assessment of these metabolites vs. a panel of micro-organisms revealed that only 184 had good antifungal potential vs. C. neoformans (IC50 4.9 µg/mL) [68].
New metabolites, emeriones A-C (190–192), were purified from an EtOH extract of the culture broth of endophytic E. nidulans, obtained from Whitmania pigra by SiO2/Sephadex LH-20/HPLC. These metabolites are high-methylated polyketides with 3,6-dioxabicyclo[3.1.0]hexane and bicyclo[4.2.0]octene functionalities and were characterized using spectroscopic, X-ray, and CD analyses as well as ECD calculations. Compounds 190 and 191 are similar but differ in their configuration at the C9, C12, and C13 epoxy rings, possessing 2R/3R/4S/5S/8R/9S/12R/13S/14S/15S/16S/17R and 2R/3R/4S/5S/8S/9R/12S/13R/14R/15R/16S/17R configurations, respectively. Moreover, 192 has an extra peroxide bridge that results in an unusual 7,8-dioxatricyclo[4.2.2.02,5]decene scaffold construction. The NO production inhibitory efficacy of 190 and 191 was tested on LPS-mediated NO production in RAW264.7 using a CCK-8 assay. Interestingly, 190 demonstrated inhibition potential vs. NO production with a percent inhibition of NO production of 68.3% at a concentration of 10.0 μM, compared to indomethacin (with a percent inhibition of NO production of 84.2%, Conc. 40 μM); however, 191 had no effectiveness, although it possesses the same structure as 190 and differs only in the bicyclo[4.2.0]octane core absolute configuration [80]. They were assumed to be synthesized from methylmalonyl CoA (9 molecules) and acetyl-CoA (one molecule) by polyketide synthase to produce I (Scheme 7), which generates II via a Payne rearrangement that features a 3,6-dioxabicyclo[3.1.0]hexane moiety (Scheme 7).
An octatomic ring is then formed through 8π electrocyclization and double bond isomerization to produce IV and V, which undergo 6π electrocyclizations to yield VI and VII, with a pair of mirror-image bicyclo[4.2.0]-octene frameworks. Further, 190 and 191 are created through an additional C-12 double bond epoxidation, while 192 is formed through a Diels–Alder reaction between an O2 molecule and a bicyclo[4.2.0]octene core (Scheme 7) [80].

3.9. Other Metabolites

Asperbenzaldehyde (199) with an aromatic ring represents a new class of metabolites with tau aggregation inhibition potential. Moreover, its modified derivatives displayed noticeable lipoxygenase inhibition, suggesting its derived metabolites could exhibit dual activity [54].
The mycelia acetone extract of mutant A. nidulans LO2955 cultured on liquid lactose produced 202 (amount ≈200 mg/L), which was not found in such amounts in the wild strain culture. This compound had lipoxygenase-1 inhibition (IC50 97.2 μM) [42].
Asperoxide A (206), a new acyclic peroxide analog, and 203 were biosynthesized by A. nidulans SD531 obtained from cold spring, deep-sea sediment in the South China Sea by SiO2/RP-18 CC and characterized by NMR and MS analyses [31] (Figure 20, Table 14). Their antimicrobial potential was examined vs. various aquatic/human bacteria and pathogenic plant fungi using a serial dilution technique. Compound 206 demonstrated antimicrobial effectiveness vs. V. harveyi, A. hydrophilia, V. parahaemolyticus, and E. tarda (MICs ranged from 16 to 64 μg/mL) [31].

4. Bioactivities of A. nidulans Extracts

The extract of E. nidulans var. acristata displayed cytotoxic potential vs. different cell lines (mean IC70 of 8.30 µg/mL) [43]. A. nidulans EtOAc extract culture broth had only moderate antibacterial effectiveness vs. B. megaterium [47]. It also (Conc. 30 μg/disc) exhibited selectivity vs. HEP-G2, compared with CCRF-CEM and CFU-GM, and potent inhibitory activity vs. HCV NS3/4A protease (IC50 30.0 μg/mL) [47]. Rhizophora stylosa-associated A. nidulans MA-143 exhibited antibacterial and brine shrimp lethality potential [34]. E. nidulans MFW39 mycelium extract (IC50 21.9 μg/mL) was found to have a more potent cytotoxic effect vs. the T47D cell line than broth extract (IC50 169.3 μg/mL) [36]. Nyctanthes arbor-tristis-associated A. nidulans extracts and fractions had moderate to potent growth inhibitory potential against NCI-H460, MCF-7, and HeLa cell lines in the SRB, where broth extract (LC50 95.0 and IC50 10.0 μg/mL) was most potent vs. HeLa, whereas mycelium petroleum ether insoluble fraction was most powerful vs. MCF-7 and NCI-H460 (IC50 18.0 and 10.0 μg/mL, respectively) [53].

5. Importance of A. nidulans and Its Enzymes

Enzymes have attracted growing interest because of their prevalent industrial applications in various fields, including pharmaceuticals, food, chemicals, and energy [81]. They can provide a cost-efficient and more efficacious process for industrial manufacturing, in comparison to chemical catalysts, since they are quite specific, eco-friendly, and function under mild conditions [82]. Therefore, there is a marked research direction towards producing enzymes with high yields to fulfill the increased industrial demand, as well as reducing the costs of enzyme production medium, isolation, and purification. In this regard, interest has been directed towards fungi as a prolific pool of enzymes.
In 2020, a review by Kumar summarized the published studies on the potential of A. nidulans as a producer of varied enzymes that have applications in diverse industrial processes [28]. Thus, in this work, the recent reports on A. nidulans’s enzymes are highlighted.
Two genes encoding β-isopropyl-malate dehydrogenase and six genes encoding BCAA (branched-chain amino acids; isoleucine, leucine, and valine) aminotransferase, which catalyze the leucine penultimate step and the BCAA final step biosynthesis, respectively, were identified utilizing A. nidulans genome sequence searches [83]. Fungal biosynthesis of BCAA is substantial enough for these fungi to cause disease in plants and human hosts. It is worth mentioning that humans lack the enzymes accountable for BCAA production; therefore, these enzymes could be a potential target of antifungal agents.

5.1. Aryl Alcohol Oxidase

AAO (Aryl alcohol oxidase) is an H2O2-providing extracellular enzyme that belongs to the glucose–ethanol–choline oxidoreductase. It converts aromatic alcohols to aldehydes and provides H2O2 for peroxidases to degrade lignin [84]; hence, it has a considerable function in lignin depolymerization, particularly in lignin polymer oxidation for the generation of fuels and chemicals [85].
A cost-effective medium for AAO high-yield production by recombinant A. nidulans was developed in a submerged culture that consisted of CSL (corn steep liquor), which is an inexpensive and rich source of nitrogen, vitamins, and minerals, in addition to NaNO3 (13.8 g/L), CSL (26.4 g/L), and maltose (61.0 g/L). It was observed that the highest achieved AAO capacity was 1021 U/L, with a 0.75 g/L protein concentration [86].

5.2. Laccases

Laccases, belonging to the multi-copper oxidase family, accelerate the O2 four-electron reduction to water with diverse non-phenolic and phenolic compound oxidation [16,87,88,89]. These features give them varied industrial applicability, including wine stabilization, denim-bleaching, detoxification and decolorization of dye-containing textiles and lignin-linked compound effluents, and pulp bio-bleaching for the paper industry [16,87,88,89].
From A. nidulans TTF-6, purified and crude laccases were employed to decolorize different dyes (e.g., methyl orange, Congo red, Victoria blue, methyl red, methyl violet, bromophenol blue, and Coomassie blue). At 40 °C, it was found that the crude enzyme needed a longer time treatment time (7 days) in comparison to the purified one (up to 48 h). Among the tested dyes, methyl red (azo dye) was taken away slowly relative to Victoria and Coomassie blue (blue-triphenylamines). A high decolorizing rate was noted at 40 °C compared to 20 °C [90].

5.3. Pectate Lyases and Nitroreductases

Pectin, a primary component of fibers, vegetables, cereals, and fruits, has a high molecular weight and is a complicated, acidic- and heterogeneous-structured polysaccharide that is hydrolyzed by pectinolytic enzymes. These enzymes have assorted industrial applicability in wine and fruit juice liquefaction, extraction, and clarification; in the fabric industry for separating plant fibers such as jute, flax, and hemp; in cotton fabric bio-preparation; in paper manufacture, treating paper and pulp mill effluents; and in amending black tea’s quality [91]. These enzymes represent 25% of the global sales of food enzymes [92]. Among them, pectate lyases act on the pectate core internal α-1,4-linkage, having a crucial function in pectin breaking down.
In 2022, AnPL9 pectate lyase, a member of PL9 (polysaccharide-lyase family-9), was characterized and purified from A. nidulans that was expressed in Pichia pastoris [93]. It is the first stated fungi derived from the PL9 pectate lyase family. AnPL9 revealed high potential on GH (homogalacturonan), the pectin from apple and citrus peel. It converted tetra-galacturonic acid to digalact-uronic acid and 4,5-unsaturated digalacturonic acid. Additionally, AnPL9 possessed marked stability at 6–11 pH with a more than 4 polymerization degree of HG oligo-saccharides, indicating AnPL9 is beneficial for bio-technological usage in paper, food, and textile manufacturing [93].
Nitroreductases are implicated in nitro-heterocyclic and -aromatic compounds and quinone reduction. They have received marked attention for their usage in environmental pollutant biodegradation [94]. It was reported that A. nidulans produced nitroreductase boosted by menadione [95].

5.4. Xylanases

Xylanases are accountable for hydrolyzing xylan by cleaving the β-1,4 link, which is a main constituent of hemicellulose. They have remarkable applicability in various fields, such as food, paper and pulp, and bio-fuel industries, as well as in effluent and agro-waste treatment.
A study reported that optimized xylanase (1250 U/mL) production, with a productivity of 313 U/mL/day by recombinant A. nidulans in a 3 L stirred tank reactor, was a 400 rpm agitation rate and 2 vvm aeration rate utilizing batch fermentation. Further, the enzyme production elevated to 327 U/mL/day and 373 U/mL/day and maximum capacity increased to 1410 and 1572 U/mL, respectively, with repeated-batch and fed-batch fermentation, respectively [96].

5.5. Meta-Cresol Production

meta-Cresol is an industrially beneficial compound that is mainly generated by chemical means from fossil sources. It has been widely employed for farm chemicals, spices, dyes, and medicine production [97]. It is also a synthetic precursor for thymol, alpha-tocopherol, menthol, fenthion, sumithion, permethrin, diphenylamine, pressure-sensitive fuel, resin plasticizer, eikonogen, etc. Its mainstream production strategies involve extraction from coal tar and chemical means as cumene acidolysis and toluene-chlorination hydrolysis [98]. However, these strategies have apparent disadvantages: tiresome but unavoidable steps of m-cresol separation from the p-, m-, and o-cresol mixtures, environmental pollution, high costs, and less purity and titer [99].
The m-cresol overproduction utilizing modified A. nidulans FGSC no. A1145∆ST∆EM was reported, which gave a gram-level titer utilizing starch (carbon source) [97]. Various strategies were carried out to increase m-cresol production, such as gene multiplication and promotor engineering, resulting in an increase to m-cresol production titers of 1.29 g/L and 2.03 g/L in shaking flasks and fed-batch culture, respectively. A. nidulans A1145∆ST∆EM possessed better resistance to m-cresol than yeast, as it grew in the liquid medium, producing up to 2.5 g/L m-cresol. Thus, A. nidulans could be further engineered for m-cresol bio-production for industrial purposes [97].

5.6. Nanoparticles Synthesis

Metallic oxide NPs (nanoparticles) have extreme usage in supercapacitors, devices, batteries, and biosensors. Vijayanandan and Balakrishnan reported that A. nidulans is an efficient fungus for the synthesis of Co3O4 (cobalt oxide) NPs [100].
Additionally, the Co3O4 nanofluid synthesized employing Nothapodytes foetida-associated A. nidulans possessed good SAR (specific absorption rate), photothermal conversion efficiency, and a greater temperature gradient than water. The good solar energy absorption ability of this nanofluid indicates its convenience for direct-absorption solar thermal energy systems [101].

6. Conclusions

In the present work, 206 metabolites of varied classes, including different types of alkaloids, xanthines, quinones, depsidones, lactones, benzophenones, furanones, terpenoids, sterols, cerebrosides, fatty acids, polyketides, and others were characterized from A. nidulans and its teleomorph from 1953 to November 2022. The fungus has been collected from various sources, such as sea sediments, sponges, ascidians, algae, endophytes, soil, worms, and cultures.
Notably, a great number of metabolites were described in 2019 (39 compounds), 2013 (34 compounds), and 2016 (30 compounds).
Alkaloids of diverse types are the main metabolites reported from this fungus. They have been investigated for different biocapacities, such as antimicrobial, cytotoxic, anti-inflammation, antioxidant, antiviral, and Erα activities. Although there is a large number of reported metabolites, a limited number of them have been evaluated for their bioactivities.
Compounds 136 and 137 provide promising target molecules for further research as ERα (estrogen receptor α) inhibitors. Interestingly, 25 and 30 demonstrated marked tau aggregation inhibitory potential; therefore, they could be lead compounds for developing tau aggregation inhibitors in Alzheimer’s disease and neurodegenerative tauopathies. Additionally, 36, 56, and 92 had potent antimicrobial potential as lead metabolites for antimicrobial agents. Moreover, 83, 84, 93, 95, and 104 revealed marked cytotoxic efficacies vs. different cell lines. Further in vivo and mechanistic investigations to elucidate and validate possible mechanisms for the active metabolites are needed, exploring the possible bioactivities of unevaluated metabolites using molecular dynamic and docking investigation.
It was found that metabolic-biosynthesis pathway engineering revealed the usefulness of creating profuse numbers of fascinating metabolites. Additionally, modifying the culture parameters and conditions affected metabolite production, such as ethanol stress. Several studies reported the usage of silent gene activation strategies, such as optimizing culture conditions (O2 concentration, pH, and temperature), adding chemical elicitors (e.g., HDACi), and co-culturing with other microbes. These strategies could open a new direction for regulating the production of metabolites and play a pronounced role in elucidating cryptic natural metabolites that will assist in the future discovery of new metabolites. Further investigation of biosynthetic pathways of these metabolites is a prerequisite for allowing the reasonable engineering or refactoring of these pathways for industrial purposes. In addition, identifying genes accountable for these metabolites’ formation could provide a chance for exploring the genetic potential of this fungus to discover novel metabolites. Therefore, using combined techniques such as genome mining, bio-informatics, fusion PCR, CRISPR (Clustered-Regularly-Interspaced Short-Palindromic Repeats), expression profiling, and culture manipulation has become progressively efficient in discovering and activating silent clusters in A. nidulans [102].

Author Contributions

Conceptualization, S.R.M.I. and G.A.M.; methodology, S.R.M.I., G.A.M. and S.G.A.M.; software, S.A.F. and K.F.G.; writing—original draft preparation, S.R.M.I., S.G.A.M. and G.A.M.; writing—review and editing, S.R.M.I., G.A.M., S.A.F. and K.F.G. resources, S.A.F. and K.F.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

BEL-7402Human hepatocellular carcinoma cell line
C28Human colon Cell Line
CCRF-CEMHuman leukemia cell line
CCK-8Cell counting kit-8
CDCircular dichroism
ECDElectronic circular dichroism
EtOHEthanol
EtOAcEthyl acetate
H-125Human lung cancer cell line
HCT-116Human colon cancer cell line
HepG2Human hepatocellular liver carcinoma cell line
HeLaHuman cervical epitheloid carcinoma cell line
HL-60Human promyelocytic leukemia cell line
HPLCHigh-performance liquid chromatography
IC50Half-maximal inhibitory concentration
K562Human myelocytic leukemia cell line
KBHuman oral epidermoid carcinoma cell line
L1210Mouse lymphocytic leukemia cell line
LD50Half maximal lethal concentration
LPSLipopolysaccharide
MCF-7Human breast adenocarcinoma cell line
MDA-MB-231Human breast cancer cell line
MICMinimum inhibitory concentrations
MSMass spectrometry
MTT3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
NCI-H460Human lung cancer cell line
NMRNuclear magnetic resonance
NONitric oxide
PC12Rat brain cancer cell line
RP-18Reversed phase-18
SRBSulforhodamine B
SiO2 CCSilica gel column chromatography
T47DHuman breast cancer cell line
TLCThin layer chromatography
WiDrHuman colon adenocarcinoma cell line

References

  1. Meyer, V.; Andersen, M.R.; Brakhage, A.A.; Braus, G.H.; Caddick, M.X.; Cairns, T.C.; de Vries, R.P.; Haarmann, T.; Hansen, K.; Hertz-Fowler, C. Current Challenges of Research on Filamentous Fungi in Relation to Human Welfare and a Sustainable Bio-Economy: A White Paper. Fungal Biol. Biotechnol. 2016, 3, 6. [Google Scholar] [CrossRef] [Green Version]
  2. Meyer, V.; Basenko, E.Y.; Benz, J.P.; Braus, G.H.; Caddick, M.X.; Csukai, M.; De Vries, R.P.; Endy, D.; Frisvad, J.C.; Gunde-Cimerman, N. Growing a Circular Economy with Fungal Biotechnology: A White Paper. Fungal Biol. Biotechnol. 2020, 7, 5. [Google Scholar] [CrossRef] [Green Version]
  3. Ibrahim, S.R.; Choudhry, H.; Asseri, A.H.; Elfaky, M.A.; Mohamed, S.G.; Mohamed, G.A. Stachybotrys Chartarum—A Hidden Treasure: Secondary Metabolites, Bioactivities, and Biotechnological Relevance. J. Fungi 2022, 8, 504. [Google Scholar] [CrossRef] [PubMed]
  4. El-Agamy, D.S.; Ibrahim, S.R.; Ahmed, N.; Khoshhal, S.; Abo-Haded, H.M.; Elkablawy, M.A.; Aljuhani, N.; Mohamed, G.A. Aspernolide F, as a New Cardioprotective Butyrolactone Against Doxorubicin-Induced Cardiotoxicity. Int. Immunopharmacol. 2019, 72, 429–436. [Google Scholar] [CrossRef]
  5. Ibrahim, S.R.; Elkhayat, E.S.; Mohamed, G.A.; Khedr, A.I.; Fouad, M.A.; Kotb, M.H.; Ross, S.A. Aspernolides F and G, New Butyrolactones from the Endophytic Fungus Aspergillus terreus. Phytochem. Lett. 2015, 14, 84–90. [Google Scholar] [CrossRef]
  6. Chen, S.; Cai, R.; Liu, Z.; Cui, H.; She, Z. Secondary metabolites from mangrove-associated fungi: Source, chemistry and bioactivities. Nat. Prod. Rep. 2022, 39, 560–595. [Google Scholar] [CrossRef] [PubMed]
  7. Ibrahim, S.R.; Mohamed, S.G.; Sindi, I.A.; Mohamed, G.A. Biologically Active Secondary Metabolites and Biotechnological Applications of Species of the Family Chaetomiaceae (Sordariales): An Updated Review from 2016 to 2021. Mycol. Progress 2021, 20, 595–639. [Google Scholar] [CrossRef]
  8. Rustamova, N.; Bozorov, K.; Efferth, T.; Yili, A. Novel secondary metabolites from endophytic fungi: Synthesis and biological properties. Phytochem. Rev. 2020, 19, 425–448. [Google Scholar] [CrossRef]
  9. Ibrahim, S.R.; Bagalagel, A.A.; Diri, R.M.; Noor, A.O.; Bakhsh, H.T.; Muhammad, Y.A.; Mohamed, G.A.; Omar, A.M. Exploring the Activity of Fungal Phenalenone Derivatives as Potential CK2 Inhibitors using Computational Methods. J. Fungi 2022, 8, 443. [Google Scholar] [CrossRef]
  10. Ibrahim, S.R.; Sirwi, A.; Eid, B.G.; Mohamed, S.G.; Mohamed, G.A. Fungal depsides—Naturally Inspiring Molecules: Biosynthesis, Structural Characterization, and Biological Activities. Metabolites 2021, 11, 683. [Google Scholar] [CrossRef]
  11. Ibrahim, S.R.M.; Fadil, S.A.; Fadil, H.A.; Eshmawi, B.A.; Mohamed, S.G.A.; Mohamed, G.A. Fungal Naphthalenones; Promising Metabolites for Drug Discovery: Structures, Biosynthesis, Sources, and Pharmacological Potential. Toxins 2022, 14, 154. [Google Scholar] [CrossRef] [PubMed]
  12. Ibrahim, S.R.M.; Mohamed, G.A.; Al Haidari, R.A.; Zayed, M.F.; El-Kholy, A.A.; Elkhayat, E.S.; Ross, S.A. Fusarithioamide B, a New Benzamide Derivative from the Endophytic Fungus Fusarium Chlamydosporium with Potent Cytotoxic and Antimicrobial Activities. Bioorg. Med. Chem. 2018, 26, 786–790. [Google Scholar] [CrossRef]
  13. Ibrahim, S.R.; Abdallah, H.M.; Elkhayat, E.S.; Al Musayeib, N.M.; Asfour, H.Z.; Zayed, M.F.; Mohamed, G.A. Fusaripeptide A: New Antifungal and Anti-Malarial Cyclodepsipeptide from the Endophytic Fungus Fusarium sp. J. Asian Nat. Prod. Res. 2018, 20, 75–85. [Google Scholar] [CrossRef] [PubMed]
  14. Ortega, H.E.; Torres-Mendoza, D.; Caballero E., Z.; Cubilla-Rios, L. Structurally uncommon secondary metabolites derived from endophytic fungi. J. Fungi 2021, 7, 570. [Google Scholar] [CrossRef] [PubMed]
  15. Ibrahim, S.R.M.; Sirwi, A.; Eid, B.G.; Mohamed, S.G.A.; Mohamed, G.A. Bright Side of Fusarium Oxysporum: Secondary Metabolites Bioactivities and Industrial Relevance in Biotechnology and Nanotechnology. J. Fungi 2021, 7, 943. [Google Scholar] [CrossRef]
  16. Hareeri, R.H.; Aldurdunji, M.M.; Abdallah, H.M.; Alqarni, A.A.; Mohamed, S.G.A.; Mohamed, G.A.; Ibrahim, S.R.M. Aspergillus Ochraceus: Metabolites, Bioactivities, Biosynthesis, and Biotechnological Potential. Molecules 2022, 27, 6759. [Google Scholar] [CrossRef]
  17. Klich, M.A. Health Effects of Aspergillus in Food and Air. Toxicol. Ind. Health 2009, 25, 657–667. [Google Scholar] [CrossRef]
  18. Bennett Scott, E.; Bakerand Joan, W. An Overview of the Genus Aspergillus. In The Aspergilli; CRC Press: Boca Raton, FL, USA, 2007; pp. 23–34. [Google Scholar]
  19. Frisvad, J.C.; Møller, L.L.H.; Larsen, T.O.; Kumar, R.; Arnau, J. Safety of the Fungal Workhorses of Industrial Biotechnology: Update on the Mycotoxin and Secondary Metabolite Potential of Aspergillus Niger, Aspergillus Oryzae, and Trichoderma Reesei. Appl. Microbiol. Biotechnol. 2018, 102, 9481–9515. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  20. Ibrahim, S.R.; Mohamed, G.A.; Khedr, A.I. Γ-Butyrolactones from Aspergillus Species: Structures, Biosynthesis, and Biological Activities. Nat. Prod. Commun. 2017, 12, 791–800. [Google Scholar] [CrossRef] [Green Version]
  21. Zhang, X.; Li, Z.; Gao, J. Chemistry and Biology of Secondary Metabolites from Aspergillus Genus. Nat. Prod. J. 2018, 8, 275–304. [Google Scholar] [CrossRef]
  22. Abdel-Azeem, A.M.; Abdel-Azeem, M.A.; Abdul-Hadi, S.Y.; Darwish, A.G. Aspergillus: Biodiversity, ecological significances, and industrial applications. In Recent Advancement in White Biotechnology through Fungi; Springer: Berlin/Heidelberg, Germany, 2019; pp. 121–179. [Google Scholar]
  23. Romero, S.M.; Giudicessi, S.L.; Vitale, R.G. Is the Fungus Aspergillus a Threat to Cultural Heritage? J. Cult. Herit. 2021, 51, 107–124. [Google Scholar] [CrossRef]
  24. Ahluwalia, S.K.; Matsui, E.C. Indoor Environmental Interventions for Furry Pet Allergens, Pest Allergens, and Mold: Looking to the Future. J. Allergy Clin. Immunol. Pract. 2018, 6, 9–19. [Google Scholar] [CrossRef]
  25. Segal, B.H.; DeCarlo, E.S.; Kwon-Chung, K.J.; Malech, H.L.; Gallin, J.I.; Holland, S.M. Aspergillus Nidulans Infection in Chronic Granulomatous Disease. Medicine 1998, 77, 345–354. [Google Scholar] [CrossRef]
  26. Henriet, S.S.; Verweij, P.E.; Warris, A. Aspergillus Nidulans and Chronic Granulomatous Disease: A Unique Host–pathogen Interaction. J. Infect. Dis. 2012, 206, 1128–1137. [Google Scholar] [CrossRef] [PubMed]
  27. Tavakoli, M.; Hedayati, M.T.; Mirhendi, H.; Nouripour-Sisakht, S.; Hedayati, N.; Saghafi, F.; Mamishi, S. The First Rare and Fatal Case of Invasive Aspergillosis of Spinal Cord due to Aspergillus Nidulans in an Iranian Child with Chronic Granulomatosis Disease: Review of Literature. Curr. Med. Mycol. 2020, 6, 55. [Google Scholar] [CrossRef]
  28. Kumar, A. Aspergillus nidulans: A Potential Resource of the Production of the Native and Heterologous Enzymes for Industrial Applications. Int. J. Microbiol. 2020, 2020, 8894215. [Google Scholar] [CrossRef]
  29. Brandl, J.; Andersen, M.R. Aspergilli: Models for Systems Biology in Filamentous Fungi. Curr. Opin. Syst. Biol. 2017, 6, 67–73. [Google Scholar] [CrossRef]
  30. Yang, S.; Li, X.; Xu, G.; Li, X.; An, C.; Wang, B. Antibacterial Anthraquinone Derivatives Isolated from a Mangrove-Derived Endophytic Fungus Aspergillus nidulans by Ethanol Stress Strategy. J. Antibiot. 2018, 71, 778–784. [Google Scholar] [CrossRef]
  31. Lü, F.; Li, X.; Chi, L.; Meng, L.; Wang, B. A New Acyclic Peroxide from Aspergillus nidulans SD-531, a Fungus obtained from Deep-Sea Sediment of Cold Spring in the South China Sea. J. Oceanol. Limnol. 2020, 38, 1225–1232. [Google Scholar] [CrossRef]
  32. Ninomiya, A.; Urayama, S.; Hagiwara, D. Antibacterial Diphenyl Ether Production Induced by Co-Culture of Aspergillus nidulans and Aspergillus fumigatus. Appl. Microbiol. Biotechnol. 2022, 106, 4169–4185. [Google Scholar] [CrossRef] [PubMed]
  33. Li, Q.; Chen, C.; He, Y.; Wei, M.; Cheng, L.; Kang, X.; Wang, J.; Hao, X.; Zhu, H.; Zhang, Y. Prenylated Quinolinone Alkaloids and Prenylated Isoindolinone Alkaloids from the Fungus Aspergillus nidulans. Phytochemistry 2020, 169, 112177. [Google Scholar] [CrossRef] [PubMed]
  34. An, C.; Li, X.; Luo, H.; Li, C.; Wang, M.; Xu, G.; Wang, B. 4-Phenyl-3, 4-Dihydroquinolone Derivatives from Aspergillus nidulans MA-143, an Endophytic Fungus Isolated from the Mangrove Plant Rhizophora stylosa. J. Nat. Prod. 2013, 76, 1896–1901. [Google Scholar] [CrossRef]
  35. An, C.; Li, X.; Li, C.; Wang, M.; Xu, G.; Wang, B. Aniquinazolines A–D, Four New Quinazolinone Alkaloids from Marine-Derived Endophytic Fungus Aspergillus nidulans. Mar. Drugs 2013, 11, 2682–2694. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Nursid, M.; Ekowati, C.; Murwantoko; Wahyuono, S. Isolation and Identification of Emestrin from Emericella nidulans and Investigation of its Anticancer Properties. Microbiol. Indones. 2011, 5, 3. [Google Scholar] [CrossRef]
  37. Nursid, M.; Namirah, I.; Cahyana, A.H.; Fajarningsih, N.D.; Chasanah, E. Emestrin B: Epipolythiodioxypiperazine from Marine Derived Fungus Emericella nidulans. J. Med. Bioeng. 2015, 4, 441–445. [Google Scholar] [CrossRef] [Green Version]
  38. Zhang, P.; Li, X.; Li, X.; Wang, B. New Indole-Diterpenoids from the Algal-Associated Fungus Aspergillus nidulans. Phytochem. Lett. 2015, 12, 182–185. [Google Scholar] [CrossRef]
  39. Zhou, H.; Sun, X.; Li, N.; Che, Q.; Zhu, T.; Gu, Q.; Li, D. Isoindolone-Containing Meroperpenoids from the Endophytic Fungus Emericella nidulans HDN12–249. Org. Lett. 2016, 18, 4670–4673. [Google Scholar] [CrossRef]
  40. Li, Q.; Chen, C.; Wei, M.; Dai, C.; Cheng, L.; Tao, J.; Li, X.; Wang, J.; Sun, W.; Zhu, H. Niduterpenoids A and B: Two Sesterterpenoids with a Highly Congested Hexacyclic 5/5/5/5/3/5 Ring System from the Fungus Aspergillus nidulans. Org. Lett. 2019, 21, 2290–2293. [Google Scholar] [CrossRef]
  41. Li, Q.; Zheng, Y.; Fu, A.; Wei, M.; Kang, X.; Chen, C.; Zhu, H.; Zhang, Y. 30-Norlanostane Triterpenoids and Steroid Derivatives from the Endophytic Fungus Aspergillus nidulans. Phytochemistry 2022, 201, 113257. [Google Scholar] [CrossRef]
  42. Somoza, A.D.; Lee, K.; Chiang, Y.; Oakley, B.R.; Wang, C.C. Reengineering an Azaphilone Biosynthesis Pathway in Aspergillus nidulans to Create Lipoxygenase Inhibitors. Org. Lett. 2012, 14, 972–975. [Google Scholar] [CrossRef] [Green Version]
  43. Sanchez, J.F.; Entwistle, R.; Hung, J.; Yaegashi, J.; Jain, S.; Chiang, Y.; Wang, C.C.; Oakley, B.R. Genome-Based Deletion Analysis Reveals the Prenyl Xanthone Biosynthesis Pathway in Aspergillus nidulans. J. Am. Chem. Soc. 2011, 133, 4010–4017. [Google Scholar] [CrossRef] [Green Version]
  44. Pockrandt, D.; Ludwig, L.; Fan, A.; König, G.M.; Li, S. New Insights into the Biosynthesis of Prenylated Xanthones: Xptb from Aspergillus nidulans Catalyses an O-Prenylation of Xanthones. Chembiochem 2012, 13, 2764–2771. [Google Scholar] [CrossRef] [PubMed]
  45. Kralj, A.; Kehraus, S.; Krick, A.; Eguereva, E.; Kelter, G.; Maurer, M.; Wortmann, A.; Fiebig, H.; König, G.M. Arugosins G and H: Prenylated Polyketides from the Marine-Derived Fungus Emericella nidulans Var. a Cristata. J. Nat. Prod. 2006, 69, 995–1000. [Google Scholar] [CrossRef] [PubMed]
  46. Kawahara, N.; Sekita, S.; Satake, M.; Udagawa, S.; Kawai, K. Structures of a New Dihydroxanthone Derivative, Nidulalin A, and a New Benzophenone Derivative, Nidulalin B, from Emericella nidulans. Chem. Pharm. Bull. 1994, 42, 1720–1723. [Google Scholar] [CrossRef] [Green Version]
  47. Hawas, U.W.; El-Kassem, L.T.; Ahmed, E.F.; Emam, M. In-Vitro Bioassays on the Metabolites of the Fungus Emericella nidulans Isolated from the Egyptian Red Sea Algae. Egypt. Pharm. J. 2012, 11, 124. [Google Scholar]
  48. Ishida, M.; Hamasaki, T.; Hatsuda, Y. The Structure of Two New Metabolites, Emerin and Emericellin, from Aspergillus nidulans. Agric. Biol. Chem. 1975, 39, 2181–2184. [Google Scholar] [CrossRef]
  49. Yaegashi, J.; Praseuth, M.B.; Tyan, S.; Sanchez, J.F.; Entwistle, R.; Chiang, Y.; Oakley, B.R.; Wang, C.C. Molecular Genetic Characterization of the Biosynthesis Cluster of a Prenylated Isoindolinone Alkaloid Aspernidine A in Aspergillus nidulans. Org. Lett. 2013, 15, 2862–2865. [Google Scholar] [CrossRef] [Green Version]
  50. Nasr, H.M.; Hawas, U.W.; Mousa, S.A.; Alasmaey, M.; Ahmed, E.F. Isolation and Identification of Emericella nidulans Secondary Metabolites. Chem. Res. J. 2018, 3, 114–119. [Google Scholar]
  51. Aukamp, P.J.; Holzapfel, C.W. Polyhydroxyanthraquinones from Aspergillus Versicolor, Aspergillus nidulans and Bipolaris Sp. their Significance in Relation to Biogenetic Theories on Aflatoxin B1. S. Afr. J. Chem. 1970, 23, 40–56. [Google Scholar]
  52. Furukawa, T.; Fukuda, T.; Nagai, K.; Uchida, R.; Tomoda, H. Helvafuranone Produced by the Fungus Aspergillus nidulans BF0142 Isolated from Hot Spring-Derived Soil. Nat. Prod. Commun. 2016, 11, 1001–1003. [Google Scholar] [CrossRef] [Green Version]
  53. Sana, T.; Siddiqui, B.S.; Shahzad, S.; Farooq, A.D.; Siddiqui, F.; Sattar, S.; Begum, S. Antiproliferative Activity and Characterization of Metabolites of Aspergillus nidulans: An Endophytic Fungus from Nyctanthes Arbor-Tristis Linn. Against Three Human Cancer Cell Lines. Med. Chem. 2019, 15, 352–359. [Google Scholar] [CrossRef]
  54. Paranjape, S.R.; Chiang, Y.; Sanchez, J.F.; Entwistle, R.; Wang, C.C.; Oakley, B.R.; Gamblin, T.C. Inhibition of Tau Aggregation by Three Aspergillus nidulans Secondary Metabolites: 2, Ω-Dihydroxyemodin, Asperthecin, and Asperbenzaldehyde. Planta Med. 2014, 80, 77–85. [Google Scholar] [CrossRef] [Green Version]
  55. Brown, D.W.; Salvo, J.J. Isolation and Characterization of Sexual Spore Pigments from Aspergillus nidulans. Appl. Environ. Microbiol. 1994, 60, 979–983. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. Grau, M.F.; Entwistle, R.; Oakley, C.E.; Wang, C.C.; Oakley, B.R. Overexpression of an LaeA-Like Methyltransferase Upregulates Secondary Metabolite Production in Aspergillus nidulans. ACS Chem. Biol. 2019, 14, 1643–1651. [Google Scholar] [CrossRef]
  57. Lin, H.; Lyu, H.; Zhou, S.; Yu, J.; Keller, N.P.; Chen, L.; Yin, W. Deletion of a Global Regulator LaeB Leads to the Discovery of Novel Polyketides in Aspergillus nidulans. Org. Biomol. Chem. 2018, 16, 4973–4976. [Google Scholar] [CrossRef]
  58. Xing, C.; Wu, J.; Xia, J.; Fan, S.; Yang, X. Steroids and Anthraquinones from the Deep-Sea-Derived Fungus Aspergillus nidulans MCCC 3A00050. Biochem. Syst. Ecol. 2019, 83, 103–105. [Google Scholar] [CrossRef]
  59. Ibrahim, S.R.M.; Mohamed, G.A.; Al Haidari, R.A.; El-Kholy, A.A.; Zayed, M.F.; Khayat, M.T. Biologically Active Fungal Depsidones: Chemistry, Biosynthesis, Structural Characterization, and Bioactivities. Fitoterapia 2018, 129, 317–365. [Google Scholar] [CrossRef] [PubMed]
  60. Dean, F.M.; Robertson, A.; ROBERTS, J.C.; Raper, K.B. Nidulin and ‘Ustin’: Two Chlorine-Containing Metabolic Products of Aspergillus nidulans. Nature 1953, 172, 344. [Google Scholar] [CrossRef] [PubMed]
  61. Sierankiewicz, J.; Gatenbeck, S. A New Depsidone from Aspergillus nidulans. Acta Chem. Scand. 1972, 26, 455–458. [Google Scholar] [CrossRef] [Green Version]
  62. Scherlach, K.; Hertweck, C. Discovery of Aspoquinolones A–D, Prenylated Quinoline-2-One Alkaloids from Aspergillus nidulans, Motivated by Genome Mining. Org. Biomol. Chem. 2006, 4, 3517–3520. [Google Scholar] [CrossRef]
  63. Perry, M.J.; Makins, J.F.; Adlard, M.W.; Holt, G. Aspergillic Acids Produced by Mixed Cultures of Aspergillus Flavus and Aspergillus nidulans. J. Gen. Microbiol. 1984, 130, 319–323. [Google Scholar] [CrossRef] [Green Version]
  64. Ryan, K.L.; Akhmedov, N.G.; Panaccione, D.G. Identification and Structural Elucidation of Ergotryptamine, a New Ergot Alkaloid Produced by Genetically Modified Aspergillus nidulans and Natural Isolates of Epichloë Species. J. Agric. Food Chem. 2015, 63, 61–67. [Google Scholar] [CrossRef]
  65. Scherlach, K.; Schuemann, J.; Dahse, H.; Hertweck, C. Aspernidine A and B, Prenylated Isoindolinone Alkaloids from the Model Fungus Aspergillus nidulans. J. Antibiot. 2010, 63, 375–377. [Google Scholar] [CrossRef]
  66. McCorkindale, N.J.; Hayes, D.; Johnston, G.A.; Clutterbuck, A.J. N-Acetyl-6-Hydroxytryptophan a Natural Substrate of a Monophenol Oxidase from Aspergillus nidulans. Phytochemistry 1983, 22, 1026–1028. [Google Scholar] [CrossRef]
  67. Kaczka, E.A.; Dulaney, E.L.; Gitterman, C.O.; Woodruff, H.B.; Folkers, K. Isolation and Inhibitory Effects on KB Cell Cultures of 3′-Deoxyadenosine from Aspergillus nidulans (Eidam) Wint. Biochem. Biophys. Res. Commun. 1964, 14, 452–455. [Google Scholar] [CrossRef] [PubMed]
  68. Tarawneh, A.H.; León, F.; Radwan, M.M.; Rosa, L.H.; Cutler, S.J. Secondary Metabolites from the Fungus Emericella nidulans. Nat. Prod. Commun. 2013, 8, 1285–1288. [Google Scholar] [CrossRef] [Green Version]
  69. Henke, M.T.; Soukup, A.A.; Goering, A.W.; McClure, R.A.; Thomson, R.J.; Keller, N.P.; Kelleher, N.L. New Aspercryptins, Lipopeptide Natural Products, Revealed by HDAC Inhibition in Aspergillus nidulans. ACS Chem. Biol. 2016, 11, 2117–2123. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  70. Benz, F.; Knüsel, F.; Nüesch, J.; Treichler, H.; Voser, W.; Nyfeler, R.; Keller-Schierlein, W. Stoffwechselprodukte Von Mikroorganismen 143. Mitteilung. Echinocandin B, Ein Neuartiges Polypeptid-antibioticum Aus Aspergillus nidulans Var. Echinulatus: Isolierung Und Bausteine. Helv. Chim. Acta 1974, 57, 2459–2477. [Google Scholar] [CrossRef] [PubMed]
  71. Bromann, K.; Viljanen, K.; Moreira, V.M.; Yli-Kauhaluoma, J.; Ruohonen, L.; Nakari-Setälä, T. Isolation and Purification of Ent-Pimara-8 (14), 15-Diene from Engineered Aspergillus nidulans by Accelerated Solvent Extraction Combined with HPLC. Anal. Methods 2014, 6, 1227–1234. [Google Scholar] [CrossRef] [Green Version]
  72. Rodríguez-Urra, A.B.; Jiménez, C.; Nieto, M.I.; Rodríguez, J.; Hayashi, H.; Ugalde, U. Signaling the Induction of Sporulation Involves the Interaction of Two Secondary Metabolites in Aspergillus nidulans. ACS Chem. Biol. 2012, 7, 599–606. [Google Scholar] [CrossRef]
  73. Gealt, M.A. Isolation of Β-Amyrin from the Fungus Aspergillus nidulans. J. Gen. Microbiol. 1983, 129, 543–546. [Google Scholar] [CrossRef] [Green Version]
  74. Shapiro, B.E.; Gealt, M.A. Ergosterol and Lanosterol from Aspergillus nidulans. J. Gen. Microbiol. 1982, 128, 1053–1056. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Hamasaki, T.; Nakajima, H.; Yokota, T.; Kimura, Y. A New Metabolite, 3-Carboxy-2, 4-Diphenyl-but-2-Enoic Anhydride, Produced by Aspergillus nidulans. Agric. Biol. Chem. 1983, 47, 891–892. [Google Scholar] [CrossRef]
  76. Chiang, Y.; Oakley, C.E.; Ahuja, M.; Entwistle, R.; Schultz, A.; Chang, S.; Sung, C.T.; Wang, C.C.; Oakley, B.R. An Efficient System for Heterologous Expression of Secondary Metabolite Genes in Aspergillus nidulans. J. Am. Chem. Soc. 2013, 135, 7720–7731. [Google Scholar] [CrossRef] [Green Version]
  77. Fukuyama, K.; Katsube, Y.; Noda, A.; Hamasaki, T.; Hatsuda, Y. Absolute Configurations of Asperlin, a Metabolite of Aspergillus nidulans, and its Related Compounds. Bull. Chem. Soc. Jpn. 1978, 51, 3175–3181. [Google Scholar] [CrossRef] [Green Version]
  78. Argoudelis, A.D.; Zieserl, J.F. The Structure of U-13,933, a New Antibiotic. Tetrahedron Lett. 1966, 7, 1969–1973. [Google Scholar] [CrossRef]
  79. Mazur, P.; Meyers, H.V.; Nakanishi, K.; Champe, S.P. Structural Elucidation of Sporogenic Fatty Acid Metabolites from Aspergillus nidulans. Tetrahedron Lett. 1990, 31, 3837–3840. [Google Scholar] [CrossRef]
  80. Li, Q.; Chen, C.; He, Y.; Guan, D.; Cheng, L.; Hao, X.; Wei, M.; Zheng, Y.; Liu, C.; Li, X. Emeriones A–C: Three Highly Methylated Polyketides with Bicyclo [4.2. 0] Octene and 3, 6-Dioxabicyclo [3.1. 0] Hexane Functionalities from Emericella nidulans. Org. Lett. 2019, 21, 5091–5095. [Google Scholar] [CrossRef]
  81. Singh, R.; Kumar, M.; Mittal, A.; Mehta, P.K. Microbial Enzymes: Industrial Progress in 21st Century. 3 Biotech. 2016, 6, 174. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  82. Choi, J.; Han, S.; Kim, H. Industrial Applications of Enzyme Biocatalysis: Current Status and Future Aspects. Biotechnol. Adv. 2015, 33, 1443–1454. [Google Scholar] [CrossRef] [PubMed]
  83. Steyer, J.T.; Downes, D.J.; Hunter, C.C.; Migeon, P.A.; Todd, R.B. Duplication and Functional Divergence of Branched-Chain Amino Acid Biosynthesis Genes in Aspergillus nidulans. Mbio 2021, 12, 768. [Google Scholar] [CrossRef]
  84. Hernández-Ortega, A.; Ferreira, P.; Martínez, A.T. Fungal Aryl-Alcohol Oxidase: A Peroxide-Producing Flavoenzyme Involved in Lignin Degradation. Appl. Microbiol. Biotechnol. 2012, 93, 1395–1410. [Google Scholar] [CrossRef]
  85. Mathieu, Y.; Piumi, F.; Valli, R.; Aramburu, J.C.; Ferreira, P.; Faulds, C.B.; Record, E. Activities of Secreted Aryl Alcohol Quinone Oxidoreductases from Pycnoporus Cinnabarinus Provide Insights into Fungal Degradation of Plant Biomass. Appl. Environ. Microbiol. 2016, 82, 2411–2423. [Google Scholar] [CrossRef] [Green Version]
  86. Liu, E.; Li, M.; Abdella, A.; Wilkins, M.R. Development of a Cost-Effective Medium for Submerged Production of Fungal Aryl Alcohol Oxidase using a Genetically Modified Aspergillus nidulans Strain. Bioresour. Technol. 2020, 305, 123038. [Google Scholar] [CrossRef]
  87. Ibrahim, S.R.; Altyar, A.E.; Mohamed, S.G.; Mohamed, G.A. Genus Thielavia: Phytochemicals, Industrial Importance and Biological Relevance. Nat. Prod. Res. 2021, 36, 5108–5123. [Google Scholar] [CrossRef]
  88. Mohamed, G.A.; Ibrahim, S.R. Untapped Potential of Marine-Associated Cladosporium Species: An Overview on Secondary Metabolites, Biotechnological Relevance, and Biological Activities. Mar. Drugs 2021, 19, 645. [Google Scholar] [CrossRef]
  89. Ibrahim, S.R.M.; Mohamed, S.G.A.; Altyar, A.E.; Mohamed, G.A. Natural Products of the Fungal Genus Humicola: Diversity, Biological Activity, and Industrial Importance. Curr. Microbiol. 2021, 78, 2488–2509. [Google Scholar] [CrossRef]
  90. Sahay, S.; Chaurse, V.; Chauhan, D. Laccase from Aspergillus nidulans TTF6 Showing Pb Activation for Smaller Substrates and Dyes Remediation in all Climates. In Proceedings of the National Academy of Sciences, India Section B: Biological Sciences; Springer: Berlin/Heidelberg, Germany, 2020; Volume 90, pp. 143–150. [Google Scholar]
  91. Dutta, N.; Mukhopadhyay, A.; Dasgupta, A.K.; Chakrabarti, K. Nanotechnology Enabled Enhancement of Enzyme Activity and Thermostability: Study on Impaired Pectate Lyase from Attenuated Macrophomina Phaseolina in Presence of Hydroxyapatite Nanoparticle. PLoS ONE 2013, 8, e63567. [Google Scholar] [CrossRef] [Green Version]
  92. Oumer, O.J. Pectinase: Substrate, Production and their Biotechnological Applications. Int. J. Environ. Agric. Biotechnol. 2017, 2, 238761. [Google Scholar] [CrossRef]
  93. Suzuki, H.; Morishima, T.; Handa, A.; Tsukagoshi, H.; Kato, M.; Shimizu, M. Biochemical Characterization of a Pectate Lyase AnPL9 from Aspergillus nidulans. Appl. Biochem. Biotechnol. 2022, 194, 5627–5643. [Google Scholar] [CrossRef]
  94. Roldán, M.D.; Pérez-Reinado, E.; Castillo, F.; Moreno-Vivián, C. Reduction of Polynitroaromatic Compounds: The Bacterial Nitroreductases. FEMS Microbiol. Rev. 2008, 32, 474–500. [Google Scholar] [CrossRef] [Green Version]
  95. Zhou, Y.; Lv, H.; Li, H.; Li, J.; Yan, Y.; Liu, F.; Hao, W.; Zhou, Z.; Wang, P.; Zhou, S. Nitroreductase Increases Menadione-Mediated Oxidative Stress in Aspergillus nidulans. Appl. Environ. Microbiol. 2021, 87, 1758. [Google Scholar] [CrossRef]
  96. Abdella, A.; Segato, F.; Wilkins, M.R. Optimization of Process Parameters and Fermentation Strategy for Xylanase Production in a Stirred Tank Reactor using a Mutant Aspergillus nidulans Strain. Biotechnol. Rep. 2020, 26, e00457. [Google Scholar] [CrossRef]
  97. Wang, W.; An, C.; Yao, Y.; Meng, X.; Gao, S. De Novo Biosynthesis and Gram-Level Production of M-Cresol in Aspergillus nidulans. Appl. Microbiol. Biotechnol. 2021, 105, 6333–6343. [Google Scholar] [CrossRef]
  98. Bing, X.; Wang, Z.; Wei, F.; Gao, J.; Xu, D.; Zhang, L.; Wang, Y. Separation of M-Cresol from Coal Tar Model Oil using Propylamine-Based Ionic Liquids: Extraction and Interaction Mechanism Exploration. ACS Omega 2020, 5, 23090–23098. [Google Scholar] [CrossRef]
  99. Vrsaljko, D.; Haramija, V.; Hadži-Skerlev, A. Determination of Phenol, M-Cresol and O-Cresol in Transformer Oil by HPLC Method. Electr. Power Syst. Res. 2012, 93, 24–31. [Google Scholar] [CrossRef]
  100. Vijayanandan, A.S.; Balakrishnan, R.M. Biosynthesis of Cobalt Oxide Nanoparticles using Endophytic Fungus Aspergillus nidulans. J. Environ. Manag. 2018, 218, 442–450. [Google Scholar] [CrossRef]
  101. Vijayanandan, A.S.; Valappil, R.S.K.; Balakrishnan, R.M. Evaluation of Photothermal Properties for Absorption of Solar Energy by Co3O4 Nanofluids Synthesized using Endophytic Fungus Aspergillus nidulans. Sustain. Energy Technol. Assess. 2020, 37, 100598. [Google Scholar] [CrossRef]
  102. Caesar, L.K.; Kelleher, N.L.; Keller, N.P. In the Fungus Where it Happens: History and Future Propelling Aspergillus nidulans as the Archetype of Natural Products Research. Fungal Genet. Biol. 2020, 144, 103477. [Google Scholar] [CrossRef]
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Figure 1. Structures of benzophenones (1–10) reported from Aspergillus nidulans.
Figure 1. Structures of benzophenones (1–10) reported from Aspergillus nidulans.
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Scheme 1. Biosynthetic pathways of compounds 3, 7, 8, and 10 from chrysophanol (29) [43].
Scheme 1. Biosynthetic pathways of compounds 3, 7, 8, and 10 from chrysophanol (29) [43].
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Figure 2. Structures of xanthones (11–21) reported from Aspergillus nidulans.
Figure 2. Structures of xanthones (11–21) reported from Aspergillus nidulans.
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Scheme 2. Biosynthetic pathways of 12, 14, 16, and 17 [45].
Scheme 2. Biosynthetic pathways of 12, 14, 16, and 17 [45].
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Figure 3. Structures of quinones (22–34).
Figure 3. Structures of quinones (22–34).
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Figure 4. Structures of quinones (35–47).
Figure 4. Structures of quinones (35–47).
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Figure 5. Structures of depsidones (48–51) and biphenyl ethers (52–60).
Figure 5. Structures of depsidones (48–51) and biphenyl ethers (52–60).
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Figure 6. Structures of quinoline alkaloids (61–73).
Figure 6. Structures of quinoline alkaloids (61–73).
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Scheme 3. Biosynthetic pathways of aspoquinolones A–D (61–64) [62].
Scheme 3. Biosynthetic pathways of aspoquinolones A–D (61–64) [62].
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Figure 7. Structures of quinazolinone (74–77), pyrazine (78–81), dioxopiperazine (82 and 83), and phenazine (84) alkaloids.
Figure 7. Structures of quinazolinone (74–77), pyrazine (78–81), dioxopiperazine (82 and 83), and phenazine (84) alkaloids.
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Figure 8. Structures of indole (85–97) alkaloids.
Figure 8. Structures of indole (85–97) alkaloids.
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Figure 9. Structures of isoindole (98–110) alkaloids.
Figure 9. Structures of isoindole (98–110) alkaloids.
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Scheme 4. Biosynthetic pathways of aspernidine A (99) [49].
Scheme 4. Biosynthetic pathways of aspernidine A (99) [49].
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Scheme 5. Biosynthesis pathways of 105–110 from asperugin A or B [39].
Scheme 5. Biosynthesis pathways of 105–110 from asperugin A or B [39].
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Figure 10. Structures of other nitrogenous compound (111–113) alkaloids.
Figure 10. Structures of other nitrogenous compound (111–113) alkaloids.
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Figure 11. Structures of peptides (114–119).
Figure 11. Structures of peptides (114–119).
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Figure 12. Structures of peptides (120–125).
Figure 12. Structures of peptides (120–125).
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Figure 13. Structures of peptides (126–129).
Figure 13. Structures of peptides (126–129).
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Figure 14. Structures of peptides (130–133).
Figure 14. Structures of peptides (130–133).
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Figure 15. Structures of terpenoids (135–144).
Figure 15. Structures of terpenoids (135–144).
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Scheme 6. Biosynthesis of niduterpenoids A (136) and B (137) from GFPP [40].
Scheme 6. Biosynthesis of niduterpenoids A (136) and B (137) from GFPP [40].
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Figure 16. Structures of sterols (145–155).
Figure 16. Structures of sterols (145–155).
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Figure 17. Structures of sterols (156–167).
Figure 17. Structures of sterols (156–167).
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Figure 18. Structures of furan (168–178) and pyran (179–188) derivatives.
Figure 18. Structures of furan (168–178) and pyran (179–188) derivatives.
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Figure 19. Structures of polyketides (189–193) and glycerides (194–196).
Figure 19. Structures of polyketides (189–193) and glycerides (194–196).
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Scheme 7. Biosynthesis of emeriones A–C (190–192) [81].
Scheme 7. Biosynthesis of emeriones A–C (190–192) [81].
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Figure 20. Structures of other metabolites (197–206).
Figure 20. Structures of other metabolites (197–206).
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Table
Table 1. Biological activity of reported metabolites from Aspergillus nidulans.
Table 1. Biological activity of reported metabolites from Aspergillus nidulans.
Compound NameBiological ActivityAssay, Organism or Cell LineBiological ResultsRef.
CompoundPositive Control
Isosecosterigmatocystin (15)AntimicrobialMicroplate/Edwardsiella ictaluri16.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[30]
Serial dilution/Edwardsiella ictarda16.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[31]
Sterigmatocystin (18)AntimicrobialSerial dilution/Vibrio parahaemolyticus64.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Versicolorin C (35)AntimicrobialMicroplate/Escherichia coli1.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[30]
Microplate/Micrococcus luteus32.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[30]
Microplate/Vibrio anguillarum4.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[30]
Microplate/Vibrio alginolyticus16.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[30]
Microplate/Edwardsiella ictaluri8.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[30]
Microplate/Vibrio parahaemolyticus1.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[30]
Isoversicolorin C (36)AntimicrobialMicroplate/Escherichia coli32.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[30]
Microplate/Micrococcus luteus16.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[30]
Microplate/Vibrio vulnificus64.0 µg/mL (MIC)Chloramphenicol 8.0 µg/mL (MIC)[30]
Microplate/Vibrio alginolyticus1.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[30]
Microplate/Edwardsiella ictaluri4.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[30]
Microplate/Vibrio parahaemolyticus32.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[30]
Violaceol I (52)AntimicrobialMicrodilution/Bacillus subtilis13.0 µg/mL (MIC)Chloramphenicol 6.3 µg/mL (MIC)[32]
Violaceol II (53)AntimicrobialMicrodilution/Bacillus subtilis50 µg/mL (MIC)Chloramphenicol 6.3 µg/mL (MIC)[32]
Diorcinol (54)AntimicrobialMicrodilution/Bacillus subtilis100.0 µg/mL (MIC)Chloramphenicol 6.3 µg/mL (MIC)[32]
Cordyol C (55)AntimicrobialMicrodilution/Bacillus subtilis100.0 µg/mL (MIC)Chloramphenicol 6.3 µg/mL (MIC)[32]
Gibellulin A (56)AntimicrobialSerial dilution/Aeromonas hydrophilia4.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Colletotrichum gloeosporioides4.0 µg/mL (MIC)Amphotericin B 0.5 µg/mL (MIC)[31]
Serial dilution/Edwardsiella ictarda2.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[31]
Serial dilution/Edwardsiella tarda4.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Escherichia coli8.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio alginolyticus8.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Vibrio harvey4.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio parahaemolyticus16.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Aspoquinolone E (65)CytotoxicityMTT/HL-6029.15 µM (IC50)cis-platin 3.22 µM (IC50)[33]
MTT/A-5493.50 µM (IC50)cis-platin 13.17 µM (IC50)[33]
MTT/MCF-724.50 µM (IC50)cis-platin 22.96 µM (IC50)[33]
Aniduquinolone B (68)CytotoxicityBrine shrimp lethality/Artemia salina7.1 μM (LD50)Colchicine 88.4 μΜ (LD50)[34]
6-Deoxyaflaquinolone E (70)CytotoxicityBrine shrimp lethality/Artemia salina4.5 μM (LD50)Colchicine 88.4 μΜ (LD50)[34]
Aflaquinolone A (73)CytotoxicityBrine shrimp lethality/Artemia salina5.5 μM (LD50)Colchicine 88.4 μΜ (LD50)[34]
Aniquinazoline A (74)CytotoxicityBrine shrimp lethality/Artemia salina1.27 μM (LD50)Colchicine 88.4 μΜ (LD50)[35]
Aniquinazoline B (75)CytotoxicityBrine shrimp lethality/Artemia salina2.11 μM (LD50)Colchicine 88.4 μΜ (LD50)[35]
Aniquinazoline C (76)CytotoxicityBrine shrimp lethality/Artemia salina4.95 μM (LD50)Colchicine 88.4 μΜ (LD50)[35]
Aniquinazoline D (77)CytotoxicityBrine shrimp lethality/Artemia salina3.42 μM (LD50)Colchicine 88.4 μΜ (LD50)[35]
Glulisine A (81)AntimicrobialMicroplate/Edwardsiella ictaluri64.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[30]
Emestrin (82) MTT/T47D1.8 μg/mL (IC50)-[36]
MTT/HepG24.2 μg/mL (IC50)-
MTT/C282.6 μg/mL (IC50)-
MTT/HeLa13.8 μg/mL (IC50)-
Emestrin B (83) MTT/T47D0.16 μg/mL (IC50)-[37]
MTT/HeLa1.56 μg/mL (IC50)-
MTT/WiDrand 1.02 μg/mL (IC50)-
3,3′-Diindolylmethane (91)AntimicrobialSerial dilution/Aeromonas hydrophilia64.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Colletotrichum gloeosporioides64.0 µg/mL (MIC)Amphotericin B 0.5 µg/mL (MIC)[31]
Serial dilution/Edwardsiella tarda64.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Terrequinone A (92)AntimicrobialSerial dilution/Aeromonas hydrophilia64.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Colletotrichum gloeosporioides2.0 µg/mL (MIC)Amphotericin B 0.5 µg/mL (MIC)[31]
Serial dilution/Edwardsiella tarda16.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Escherichia coli2.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio alginolyticus2.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Vibrio harvey64.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio parahaemolyticus32.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
19-Hydroxypenitrem A (93)CytotoxicityBrine shrimp lethality/Artemia salina3.2 μM (LD50)Colchicine 10.7 μΜ (LD50)[38]
AntibacterialWell diffusion/Escherichia coli16.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[38]
Well diffusion/Edwardsiella tarda16.0 µg/mL (MIC)Chloramphenicol 16.0 µg/mL (MIC)[38]
Well diffusion/S. aureus16.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[38]
Well diffusion/Vibrio anguillarum32.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[38]
19-Hydroxypenitrem E (94)CytotoxicityBrine shrimp lethality/Artemia salina4.6 μM (LD50)Colchicine 10.7 μΜ (LD50)[38]
AntibacterialWell diffusion/Escherichia coli64.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[38]
Well diffusion/Edwardsiella tarda64.0 µg/mL (MIC)Chloramphenicol 16.0 µg/mL (MIC)[38]
Penitrem A (95)CytotoxicityBrine shrimp lethality/
ArtemiArtemia salina		1.7 μM (LD50)Colchicine 10.7 μΜ (LD50)[38]
AntibacterialWell diffusion/Escherichia coli16.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[38]
Well diffusion/Edwardsiella tarda16.0 µg/mL (MIC)Chloramphenicol 16.0 µg/mL (MIC)[38]
Well diffusion/S. aureus16.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[38]
Well diffusion/Vibrio anguillarum16.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[38]
Penijanthine A (96)CytotoxicityBrine shrimp lethality/Artemia salina8.7 μM (LD50)Colchicine 10.7 μΜ (LD50)[38]
Aspernidine G (103)CytotoxicityMTT/HL-6028.75 µM (IC50)cis-platin 3.22 µM (IC50)[33]
MTT/MCF-728.31 µM (IC50)cis-platin 22.96 µM (IC50)[33]
MTT/SW-48021.67 µM (IC50)cis platin 18.01 µM (IC50)[33]
Aspernidine H (104)CytotoxicityMTT/HL-6015.81 µM (IC50)cis-platin 3.22 µM (IC50)[33]
MTT/A-54933.03 µM (IC50)cis-platin 13.17 µM (IC50)[33]
MTT/SMMC-772117.17 µM (IC50)cis-platin 12.65 µM (IC50)[33]
MTT/MCF-717.80 µM (IC50)cis-platin 22.96 µM (IC50)[33]
MTT/SW-4804.77 µM (IC50)cis-platin 18.01 µM (IC50)[33]
Emeriphenolicin E (108)CytotoxicitySRB/HeLa4.77 µM (IC50)Adriamycin[39]
SRB/A54912.04 µM (IC50)Adriamycin[39]
SRB/HCT-11633.05 µM (IC50)Adriamycin[39]
Niduterpenoid A (136)ERα inhibitorsMCF-7/MTT11.42 µM (IC50)-[40]
(7Z,9Z,17Z)-,2α,3β-dihydroxypregna-7,9,17 (20)-trien-18-al (145)CytotoxicityMTT/PC127.34 µM (IC50)Doxorubicin 5.71 µM (IC50)[41]
Microperfuranone (173)AntimicrobialSerial dilution/Colletotrichum gloeosporioides32.0 µg/mL (MIC)Amphotericin B 0.5 µg/mL (MIC)[31]
Serial dilution/Edwardsiella ictarda4.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[31]
Serial dilution/Edwardsiella tarda32.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Escherichia coli32.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio harvey16.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio parahaemolyticus32.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
9-Hydroxymicroperfuranone (174)AntimicrobialSerial dilution/Colletotrichum gloeosporioides64.0 µg/mL (MIC)Amphotericin B 0.5 µg/mL (MIC)[31]
Serial dilution/Edwardsiella tarda32.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Escherichia coli64.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio harvey16.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Curvularin (189)AntimicrobialSerial dilution/Edwardsiella ictarda32.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[31]
6-((S,3E,5E)-5,7-Dimethyl-2-oxonona-3,5-dien-1-yl)-2,4-dihydroxy-3-methylbenzaldehyde (202)Lipoxygenase-1 inhibitionSpectrophotometric/Soybean lipoxygenase 197.2 µM (IC50)-[42]
Lecanoric acid (203)AntimicrobialSerial dilution/Aeromonas hydrophilia32.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Edwardsiella ictarda32.0 µg/mL (MIC)Chloramphenicol 2.0 µg/mL (MIC)[31]
Serial dilution/Escherichia coli16.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio harvey8.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio parahaemolyticus4.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Asperoxide A (206)AntimicrobialSerial dilution/Aeromonas hydrophilia32.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Edwardsiella tarda16.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Serial dilution/Vibrio harveyi32.0 µg/mL (MIC)Chloramphenicol 1.0 µg/mL (MIC)[31]
Serial dilution/Vibrio parahaemolyticus64.0 µg/mL (MIC)Chloramphenicol 0.5 µg/mL (MIC)[31]
Table
Table 2. Benzophenones reported from Aspergillus nidulans.
Table 2. Benzophenones reported from Aspergillus nidulans.
Compound NameMol. Wt. *Mol. Formula *Host (Part, Family)/LocationRef.
Monodictyphenone (1)288C15H12O6Cultured[44]
Arugosin F (2)272C15H12O5Cultured[45]
Arugosin H (3)356C20H20O6Cultured[45]
--Green alga, Sardinia, Italy, Mediterranean Sea[43]
Arugosin I (4)340C20H20O5Cultured[45]
Nidulalin B (5)302C16H14O6Cultured[46]
1(3H)-Isobenzofuranone, 3-(2,6-dihydroxyphenyl)-4-hydroxy-6-methyl (6)272C15H12O5Cultured[44]
Arugosin A (7)424C25H28O6Cultured[45]
--Green alga, Sardinia, Italy, Mediterranean Sea[43]
Arugosin B (8)424C25H28O6Cultured[45]
--Green alga, Sardinia, Italy, Mediterranean Sea[43]
Arugosin C (9)426C25H30O6Deep-sea sediment, South China Sea[31]
Arugosin G (10)492C30H36O6Green alga, Sardinia, Italy, Mediterranean Sea[43]
* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.
Table
Table 3. Xanthones and quinones reported from Aspergillus nidulans.
Table 3. Xanthones and quinones reported from Aspergillus nidulans.
Compound Name/Chemical ClassMol. Wt. *Mol. Formula *Host (Part, Family)/LocationRef.
Xanthones
9H-Xanthen-9-one, 8-hydroxy-1-(hydroxymethyl)-3-methyl (11)256C15H12O4Cultured[44]
Variecoxanthone A (12)340C20H20O5Cultured[44,45]
Paeciloxanthone (13)324C20H20O4Cultured[44]
Emericellin (14)408C25H28O5Cultured[44,45,48,49]
--Green alga, Sardinia, Italy, Mediterranean Sea[43]
--Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt[47,50]
Isosecosterigmatocystin (15)362C18H18O8Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[30]
--Deep-sea sediment, South China Sea[31]
Shamixanthone (16)406C25H26O5Cultured[44,45,48,49]
--Green alga, Sardinia, Italy, Mediterranean Sea[43]
--Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt[50]
Epishamixanthone (17)406C25H26O5Cultured[44,45,49]
Sterigmatocystin (18)324C18H12O6Cultured[48,49,51]
--Green alga, Sardinia, Italy, Mediterranean Sea[43]
--Soil, Hell Valley, Noboribetsu, Hokkaido, Japan[52]
--Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[30]
--Deep-sea sediment, South China Sea[31]
--Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt[47]
--Nyctanthes arbor-tristis (Oleaceae), Sabira[53]
Demethylsterigmatocystin (19)310C17H10O6Cultured[54]
1-Hydroxy-3-methylxanthone (20)226C14H10O3Nyctanthes arbor-tristis (Oleaceae), Sabira[53]
Nidulalin A (21)302C16H14O6Cultured[46]
Quinones
1,6,8-Trihydroxyxanthone (22)256C14H8O5Cultured[55]
Emodin (23)270C15H10O5Cultured[44,55]
2-Hydroxyemodin (24)286C15H10O6Cultured[56]
2,ω-Dihydroxyemodin (25)302C15H10O7Cultured[44]
ω-Hydroxyemodin (26)286C15H10O6Cultured[44]
Aloe-emodin (27)270C15H10O5Cultured[44]
Endocrocin (28)314C16H10O7Cultured[44]
Chrysophanol (29)254C15H10O4Cultured[44,45]
Asperthecin (30)318C15H10O8Cultured[49,57]
3′-Hydroxyversiconol (31)376C18H16O9Cultured[54]
Versiconol (32)360C18H16O8Cultured[56]
Averantin (33)372C20H20O7Cultured[56]
Norsolorinic acid (34)370C20H18O7Cultured[55]
--Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[30]
Versicolorin C (35)340C18H12O7Cultured[48,51]
--Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[30]
Isoversicolorin C (36)340C18H12O7Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[30]
8-O-Methylversicolorin A (37)352C19H12O7Deep-sea sediment, western Pacific Ocean, China[58]
Aversin (38)368C20H16O7Deep-sea sediment, western Pacific Ocean, China[58]
Averufin (39)368C20H16O7Cultured[48,51]
--Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[30]
6-O-Methylaverufin (40)382C21H18O7Deep-sea sediment, western Pacific Ocean, China[58]
6,8-Di-O-Methylaverufin (41)396C22H20O7Deep-sea sediment, western Pacific Ocean, China[58]
Nidurufin (42)384C20H16O8Cultured[51]
Ascoquinone A (43)618C30H18O15Cultured[55]
Averufanin (44)370C20H18O7Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[30]
Paeciloquinone E (45)368C20H16O7Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[30]
cis-Emodinphysicon-bianthrone (46)524C31H24O8Cultured[56]
trans-Emodin-physicon bianthrone (47)524C31H24O8Cultured[56]
* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.
Table
Table 4. Depsidone and diphenyl ethers reported from Aspergillus nidulans.
Table 4. Depsidone and diphenyl ethers reported from Aspergillus nidulans.
Compound Name/Chemical ClassMol. Wt. *Mol. Formula *Host (Part, Family)/LocationRef.
Depsidone
Nidulin (48)443C20H17Cl3O5Cultured[60]
Nor-nidulin (Ustin) (49)427C19H15Cl3O5Cultured[60]
Dechloro-nornidulin (50)394C19H16Cl2O5Cultured[61]
Trisdechloro-nornidulin (51)326C19H18O5Cultured[61]
Diphenyl ethers
Violaceol I (52)262C14H14O5Cultured[32]
Violaceol II (53)262C14H14O5Cultured[32]
Diorcinol (54)230C14H14O3Cultured[32]
--Soil, Hell Valley, Noboribetsu, Hokkaido, Japan[52]
--Deep-sea sediment, western Pacific Ocean, China[58]
Cordyol C (55)246C14H14O4Cultured[32]
Gibellulin A (56)360C14H12O5Deep-sea sediment, South China Sea[31]
Gibellulin C (57)274C15H14O5Cultured[57]
Gibellulin D (58)274C15H14O5Cultured[57]
F9775 A (59)396C21H16O8Cultured[54]
F9775 B (60)396C21H16O8Cultured[54]
* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.
Table
Table 5. Quinoline alkaloids reported from Aspergillus nidulans.
Table 5. Quinoline alkaloids reported from Aspergillus nidulans.
Compound NameMol. Wt. *Mol. Formula *Host (Part, Family)/LocationRef.
Aspoquinolone A (61)465C27H31NO6Cultured[62]
Aspoquinolone B (62)465C27H31NO6Cultured[62]
Aspoquinolone C (63)483C27H33NO7Cultured[62]
Aspoquinolone D (64)483C27H33NO7Cultured[62]
Aspoquinolone E (65)435C26H29NO5Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China[33]
Aspoquinolone F (66)435C26H29NO5Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China[33]
Aniduquinolone A (67)435C26H29NO5Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[34]
Aniduquinolone B (68)453C26H31NO6Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[34]
Aniduquinolone C (69)353C21H23NO4Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[34]
6-Deoxyaflaquinolone E (70)269C16H15NO3Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[34]
Isoaflaquinolone E (71)285C16H15NO4Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[34]
14-Hydroxyaflaquinolone F (72)271C15H13NO4Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[34]
Aflaquinolone A (73)433C27H31NO4Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[34]
* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.
Table
Table 6. Quinazolinone, pyrazine, dioxopiperazine, and phenazine alkaloids reported from A. nidulans.
Table 6. Quinazolinone, pyrazine, dioxopiperazine, and phenazine alkaloids reported from A. nidulans.
Compound Name/Chemical ClassMol. Wt. *Mol. Formula *Host (Part, Family)/LocationRef.
Quinazolinone alkaloids
Aniquinazoline A (74)471C26H25N5O4Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[35]
Aniquinazoline B (75)473C26H27N5O4Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[35]
Aniquinazoline C (76)489C26H27N5O5Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[35]
Aniquinazoline D (77)430C22H24N4O4Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[35]
Pyrazine alkaloids
Hydroxyaspergillic acid (78)240C12H20N2O3Cultured[63]
Neohydroxyaspergillc acid (79)240C12H20N2O3Cultured[63]
1-Hydroxy-3-sec-butyl-6-(1-hydroxy-l-methyl-propyl)
-pyrazin-2-one (80)		240C12H20N2O3Cultured[63]
Glulisine A (81)223C11H17N3O2Rhizophora stylosa (Mangrove plant fresh leaves, Rhizophoraceae)[30]
Dioxopiperazine alkaloids
Emestrin (82)598C27H22N2O10S2Soil, Hell Valley, Noboribetsu, Hokkaido, Japan[36,52]
Aplidium longithorax (Ascidin, Polyclinidae), Wakatobi Marine National Park, Southeast Sulawesi, Indonesia[36]
Emestrin B (83)630C27H22N2O10S3Aplidium longithorax (Marine Ascidin, Polyclinidae), Wakatobi Marine National Park, Southeast Sulawesi, Indonesia[37]
Phenazine alkaloids
5,10-Dihydrophenazine-1-carboxylic acid (84)226C13H10N2O2Nyctanthes arbor-tristis Linn (Oleaceae), Sabira[53]
* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.
Table
Table 7. Indole and isoindole alkaloids reported from A. nidulans.
Table 7. Indole and isoindole alkaloids reported from A. nidulans.
Compound Name/Chemical ClassMol. Wt. *Mol. Formula *Host (Part, Family)/LocationRef.
Indole alkaloids
N-Acetyl-6-hydroxy-DL-tryptophan (85)262C13H14N2O4Cultured[66]
N-Acetyl-6-benzyloxy-DL-tryptophan (86)352C20H20N2O4Cultured[66]
Ergotryptamine (87)258C16H22N2OMutant strain cultured[64]
N-methyl-4-dimethylallyltryptophan (88)286C17H22N2O2Mutant strain cultured[64]
(Z)-N-Methyl-5-(2-methylpropylidene)-1,3,4,5-tetrahydrobenzo[cd]indol-4-amine (89)240C16H20N2Mutant strain cultured[64]
(E)-N-Methyl-2-(4-(3-methylbuta-1,3-dien-1-yl)-1H-indol-3-yl)ethan-1-amine (90)240C16H20N2Mutant strain cultured[64]
3,3′-Diindolylmethane (91)246C17H30N2O3Deep-sea sediment, South China Sea[31]
Terrequinone A (92)490C32H30N2O3Deep-sea sediment, South China Sea[31]
19-Hydroxypenitrem A (93)649C37H44ClNO7Polysiphonia scopulorum var. villum (Red alga, Rhodomelaceae), Yantai, North China[38]
19-Hydroxypenitrem E (94)615C37H45NO7Polysiphonia scopulorum var. villum (Red alga, Rhodomelaceae), Yantai, North China[38]
Penitrem A (95)649C37H44ClNO7Polysiphonia scopulorum var. villum (Red alga, Rhodomelaceae), Yantai, North China[38]
Penijanthine A (96)419C27H33NO3Polysiphonia scopulorum var. villum (Red alga, Rhodomelaceae), Yantai, North China[38]
Emindole DA (97)405C28H39NOGreen alga, Sardinia, Italy, Mediterranean Sea[43]
Isoindole alkaloids
Cichorine (98)193C10H11NO3Cultured[44,57]
Aspernidine A (99)399C24H33NO4Cultured[65]
Aspernidine B (100)385C23H31NO4Cultured[65]
Aspernidine C (101)413C25H35NO4Cultured[49]
Aspernidine F (102)443C26H37NO5Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China[33]
Aspernidine G (103)413C24H31NO5Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China[33]
Aspernidine H (104)457C26H35NO6Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China[33]
Emericellolide A (105)559C30H41NO9Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China[39]
Emericellolide B (106)559C30H41NO9Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China[39]
Emericellolide C (107)545C29H39NO9Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China[39]
Emeriphenolicin E (108)733C44H63NO8Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China[39]
Emeriphenolicin F (109)733C44H63NO8Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China[39]
Emeriphenolicin G (110)747C45H65NO8Tamarix chinensis (Leaves, Tamaricaceae), Laizhou Bay, China[39]
* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.
Table
Table 8. Other nitrogenous compounds reported from A. nidulans.
Table 8. Other nitrogenous compounds reported from A. nidulans.
Compound NameMol. Wt. *Mol. Formula *Host (Part, Family)/LocationRef.
3′- Deoxyadenosine (111)251C10H13N5O3Cultured[67]
--Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt[47]
Emerin (112)316C20H16N2O2Cultured[48]
Flavuside B (113)755C43H81N7O9Piece of orange peel (Rutaceae), Tifton, Georgia[68]
* Mol. Wt.: Molecular weight; Mol. Formula: Molecular formula.
Table
Table 9. Peptides reported from A. nidulans.
Table 9. Peptides reported from A. nidulans.
Compound NameMol. Wt.Mol. FormulaHost (Part, Family)Ref.
Nidulanin A (114)603C34H45N5O5Cultured[56]
Echinocandin B (115)1059C52H81N7O16Cultured[70]
Aspercryptin A1 (116)757C37H71N7O9Mutant strain cultured[69]
Aspercryptin A2 (117)741C37H71N7O8Mutant strain cultured[69]
epi-Aspercryptin A2 (118)741C37H71N7O8Mutant strain cultured[69]
Aspercryptin A3 (119)743C36H69N7O9Mutant strain cultured[69]
Aspercryptin A4 (120)729C35H67N7O9Mutant strain cultured[69]
Aspercryptin A5 (121)727C36H69N7O8Mutant strain cultured[69]
Aspercryptin A6 (122)713C35H67N7O8Mutant strain cultured[69]
Aspercryptin A7 (123)670C34H66N6O7Mutant strain cultured[69]
Aspercryptin B1 (124)933C47H79N7O12Mutant strain cultured[69]
Aspercryptin B2 (125)917C47H79N7O11Mutant strain cultured[69]
Aspercryptin B3 (126)919C46H77N7O12Mutant strain cultured[69]
Aspercryptin B4 (127)905C45H75N7O12Mutant strain cultured[69]
Aspercryptin C1 (128)799C39H73N7O10Mutant strain cultured[69]
Aspercryptin C2 (129)783C39H73N7O9Mutant strain cultured[69]
Aspercryptin C3 (130)785C38H71N7O10Mutant strain cultured[69]
Aspercryptin C4 (131)771C37H69N7O10Mutant strain cultured[69]
Aspercryptin C6 (132)755C37H69N7O9Mutant strain cultured[69]
Aspercryptin D1 (133)813C40H75N7O10Mutant strain cultured[69]
Table
Table 10. Terpenes reported from A. nidulans.
Table 10. Terpenes reported from A. nidulans.
Compound NameMol. Wt.Mol. FormulaHost (Part, Family)/LocationRef.
ent-Pimara-8(14),15-diene (134)272C20H32Engineered cultured[71]
Neoaustinone (135)442C25H30O7Cultured[56]
Niduterpenoid A (136)404C25H40O4Whitmania pigra Whitman (Annelida, segmented worm, Hirudinidae), Hubei, China[40]
Niduterpenoid B (137)404C25H40O4Whitmania pigra Whitman (Annelida, segmented worm, Hirudinidae), Hubei, China[40]
Austin (138)500C27H32O9Cultured[72]
Dehydroaustin (139)498C27H30O9Cultured[72]
Acetoxydehydroaustin (140)556C29H32O11Cultured[72]
Austinolide (141)442C25H30O7Cultured[56]
Austinol (142)458C25H30O8Cultured[44,49,72]
--Deep-sea sediment, South China Sea[31]
Dehydroaustinol (143)456C25H28O8Cultured[44,49,72]
--Deep-sea sediment, South China Sea[31]
β-Amyrin (144)426C30H50OCultured[73]
Table
Table 11. Sterols reported from A. nidulans.
Table 11. Sterols reported from A. nidulans.
Compound NameMol. Wt.Mol. FormulaHost (Part, Family)/LocationRef.
(7Z,9Z,17Z)-,2α,3β-Dihydroxypregna-7,9,17(20)-trien-18-al (145)328C21H28O3Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China[41]
Ergosterol (146)396C28H44OCultured[41,74]
--Deep-sea sediment of the western Pacific Ocean, China[58]
--Nyctanthes arbor-tristis (Oleaceae), Sabira[53]
--Piece of orange peel (Rutaceae), Tifton, Georgia[68]
Lanosterol (147)426C30H50OCultured[74]
Nidulanoid A (148)486C30H46O5Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China[41]
Nidulanoid B (149)456C30H48O3Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China[41]
(17E,22E,24R)-3β,5α-Dihydroxyergosta-7,17,22-trien-6,16-dione (150)440C28H40O4Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China[41]
Poriferastane-3β,6α-diol (151)432C29H52O2Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China[41]
3β,5α-Dihydroxy-(22E,
24R)-ergosta-7,22-dien-6-one (152)		428C28H44O3Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China[41]
(22E,24R)-Ergosta-7,22-dien-3β,5α,6α-triol (153)430C28H46O3Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China[41]
5α,8α-Epidoxyergosta-6,22-dien-3β-ol (154)428C28H44O3Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China[41]
--Deep-sea sediment, western Pacific Ocean, China[58]
5α,8α-Epidioxyergosta-6,9(11),22-trien-3β-ol (155)426C28H42O3Deep-sea sediment, western Pacific Ocean, China[58]
--Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt[47]
(22E)-3β,4β,5α-Trihydroxyergosta-7,22-dien-6-one (156)444C28H44O4Whitmania pigra (Annelida, segmented worm, Hirudinidae), Qichun city, Hubei, China[41]
5α,6α-Epoxy-3β-hydroxy-(22E)-ergosta-8(14),22-dien-7-one (157)426C28H42O3Deep-sea sediment, western Pacific Ocean, China[58]
3β,5α,9α-Trihydroxyergosta-7,22-diene-6-one (158)444C28H44O4Deep-sea sediment, western Pacific Ocean, China[58]
3β,5α-Dihydroxy-6β-acetoxy-ergosta-7,22-diene (159)458C30H50O3Deep-sea sediment, western Pacific Ocean, China[58]
3β,5α,6β,22E-Ergosta-7,22-diene-3,5,6-triol 6-palmitate (160)668C44H76O4Deep-sea sediment, western Pacific Ocean, China[58]
Nuatigenin (161)430C27H42O4Deep-sea sediment, western Pacific Ocean, China[58]
1-Dehydronuatigenone (162)426C27H38O4Deep-sea sediment, western Pacific Ocean, China[58]
1-Dehydroisonuatigenone (163)426C27H38O4Deep-sea sediment, western Pacific Ocean, China[58]
3β,15α-Dihydroxyl-(22E,24R)-ergosta-5,8(14),22-trien-7-one (164)426C28H42O3Deep-sea sediment, western Pacific Ocean, China[58]
3β,15β-Dihydroxyl-(22E,24R)-ergosta-5,8(14),22-trien-7-one (165)426C28H42O3Deep-sea sediment, western Pacific Ocean, China[58]
β-Sitosterol-3-O-β-D-glucoside (166)576C35H60O6Piece of orange peel (Rutaceae), Tifton, Georgia[68]
Ergosterol peroxide (167)428C28H44O3Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina,
Egypt		[47]
Table
Table 12. Furan and pyran derivatives reported from A. nidulans.
Table 12. Furan and pyran derivatives reported from A. nidulans.
Compound NameMol. Wt.Mol. FormulaHost (Part, Family)Ref.
Nidulol (168)194C10H10O4Cultured[51]
Porriolide (169)194C10H10O4Cultured[57]
3-Methoxyporriolide (170)224C11H12O5Cultured[57]
7-Methoxyporriolide (171)224C11H12O5Cultured[57]
3-Carboxy-2,4-diphenyl-but-2-enoic anhydride (172)264C17H12O3Cultured[75]
Microperfuranone (173)266C17H14O3Green alga, Sardinia, Italy, Mediterranean Sea[43]
--Soil, Hell Valley, Noboribetsu, Hokkaido, Japan[52]
--Cultured[57]
--Deep-sea sediment, South China Sea[31]
9-Hydroxymicroperfuranone (174)282C17H14O4Soil, Hell Valley, Noboribetsu, Hokkaido, Japan[52]
--Deep-sea sediment, South China Sea[31]
Helvafuranone (175)298C17H14O5Soil, Hell Valley, Noboribetsu, Hokkaido, Japan[52]
Asperfuranone (176)332C19H24O5Mutant strain cultured[76]
Cichorine intermediate (177)196C10H12O4Cultured[56]
(4S,5R)-4-Hydroxy-5-methylfuran-2-one (178)132C5H8O4Piece of orange peel (Rutaceae), Tifton, Georgia[68]
Asperlin (U-13,933) (179)212C10H12O5Cultured[75,77,78]
Chloro-asperlin (180)248C10H13ClO5Cultured[77]
Versiol (181)262C16H22O3Deep-sea sediment, western Pacific Ocean, China[58]
PsiAα (182)294C18H30O3Cultured[79]
PsiAβ (183)296C18H32O3Cultured[79]
Trichodermatide B (184)264C16H24O3Piece of orange peel (Rutaceae), Tifton, Georgia[68]
Koninginin A (185)284C16H28O4Piece of orange peel (Rutaceae), Tifton, Georgia[68]
Koninginin E (186)282C16H26O4Piece of orange peel (Rutaceae), Tifton, Georgia[68]
Koninginin H (187)298C16H26O5Piece of orange peel (Rutaceae), Tifton, Georgia[68]
Asperlinol (188)230C10H14O6Cultured[77]
Table
Table 13. Polyketides and glycerides reported from A. nidulans.
Table 13. Polyketides and glycerides reported from A. nidulans.
Compound Name/Chemical ClassMol. Wt.Mol. FormulaHost (Part, Family)Ref.
Polyketides
Curvularin (189)292C16H20O5Deep-sea sediment, South China Sea[31]
Emerione A (190)472C29H44O5Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China[80]
Emerione B (191)472C29H44O5Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China[80]
Emerione C (192)488C29H44O6Whitmania pigra (Annelida, segmented worm, Hirudinidae), Hubei, China[80]
Citrantifidiol (193)240C15H28O2Piece of orange peel (Rutaceae), Tifton, Georgia[68]
Glycerides
Gingerglycolipid B (194)678C33H58O14Piece of orange peel (Rutaceae), Tifton, Georgia[68]
(2S)-bis[9Z,12Z]-1-O, 2-
O-Dilinoleoyl-3-O-[α-D-galactopyranosyl-(1″→6′) β-D-galactopyranosyl]glycerol (195)		940C51H88O15Piece of orange peel (Rutaceae), Tifton, Georgia[68]
(2S)-bis[9Z,12Z]-1-O, 2-O-dilinoleoyl-3-O-β-D-galactopyranosylglycerol (196)778C45H78O10Piece of orange peel (Rutaceae), Tifton, Georgia[68]
Table
Table 14. Other metabolites reported from A. nidulans.
Table 14. Other metabolites reported from A. nidulans.
Compound NameMol. Wt.Mol. FormulaHost (Part, Family)Ref.
Aspernidine D (197)386C24H34O4Cultured[49]
Aspernidine E (198)402C24H34O5Cultured[49]
Asperbenzaldehyde (199)316C19H24O4Cultured[54]
3-Methylorsellinic acid (200)182C9H10O4Cultured[56]
O-Methyl-3-methylorsellinaldehyde dimer (201)360C20H24O6Cultured[56]
6-((S,3E,5E)-5,7-Dimethyl-2-oxonona-3,5-dien-1-yl)-2,4-dihydroxy- 3-methylbenzaldehyde (202)316C19H24O4Mutant strain cultured[42]
Lecanoric acid (203)318C16H14O7Deep-sea sediment, South China Sea[31]
Myristic acid (204)228C14H28O2Turbinaria elatensis (Brown alga, Phaeophyceae), Egyptian Red Sea, Ras Mohamed, South Sina, Egypt[47]
Atrochrysone (205)274C15H14O5Cultured[56]
Asperoxide A (206)234C12H26O4Deep-sea sediment, South China Sea[31]
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Ghazawi, K.F.; Fatani, S.A.; Mohamed, S.G.A.; Mohamed, G.A.; Ibrahim, S.R.M. Aspergillus nidulans—Natural Metabolites Powerhouse: Structures, Biosynthesis, Bioactivities, and Biotechnological Potential. Fermentation 2023, 9, 325. https://doi.org/10.3390/fermentation9040325

AMA Style

Ghazawi KF, Fatani SA, Mohamed SGA, Mohamed GA, Ibrahim SRM. Aspergillus nidulans—Natural Metabolites Powerhouse: Structures, Biosynthesis, Bioactivities, and Biotechnological Potential. Fermentation. 2023; 9(4):325. https://doi.org/10.3390/fermentation9040325

Chicago/Turabian Style

Ghazawi, Kholoud F., Sarah A. Fatani, Shaimaa G. A. Mohamed, Gamal A. Mohamed, and Sabrin R. M. Ibrahim. 2023. "Aspergillus nidulans—Natural Metabolites Powerhouse: Structures, Biosynthesis, Bioactivities, and Biotechnological Potential" Fermentation 9, no. 4: 325. https://doi.org/10.3390/fermentation9040325

APA Style

Ghazawi, K. F., Fatani, S. A., Mohamed, S. G. A., Mohamed, G. A., & Ibrahim, S. R. M. (2023). Aspergillus nidulans—Natural Metabolites Powerhouse: Structures, Biosynthesis, Bioactivities, and Biotechnological Potential. Fermentation, 9(4), 325. https://doi.org/10.3390/fermentation9040325

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