Identification of Bioactive Compounds from Marine Actinobacteria and Fungi

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 22375

Special Issue Editors


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Guest Editor
BioC-CheM Solutions Srl, Via R. Lepetit 34, 21040 Gerenzano (Varese), Italy
Interests: microorganism; marine actinobacteria; biotechnological production; proteomics; identification; purification; quantitative
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Guest Editor
Departamento de Química y Centro de Biotecnología DAL, Universidad Técnica Federico Santa María, Valparaiso, Chile
Interests: marine actinomycetes; metabolomics; natural products; antibiotics; biosynthetic gene clusters; keratinases

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Guest Editor
Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy
Interests: actinomycetes; secondary metabolites; bioactive proteins; fermentation; isolation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,                

Microorganisms are by far the most notable and most prolific source of bioactive compounds and possess, over other producers, such as plants and animals, the advantage of being relatively easy to isolate and cultivate. Among microorganisms, actinobacteria and fungi remain an outstanding source of bioactive compounds with potential application to various fields. It is a matter of fact that the curve of discovery for new bioactive compounds has come to a near-saturation situation due to redundancy in the isolation of both microorganisms and biosynthetic pathways. However, discovery and development from unexplored environments have been proved a successful strategy when pursuing for microbial novelty. Besides a wealth of information about terrestrial actinobacteria and fungi, marine environments, which represent a large part of the Earth’s biosphere, still remain mostly unexplored. Marine environments are, therefore, inspiring the search for new bioactive molecules of interest such as nutraceuticals, proteins, and pharmaceuticals for various applications.

The goal of this Special Issue is to describe, by original research articles or reviews, the identification, characterization and production of Bioactive Compounds from Marine Actinobacteria and Fungi. The originality of the manuscripts will be established in consideration of the novelty, not only of the bioactive compounds, but also of the producer microorganisms, of the strain isolation methodology, or of the particular habitat explored. Finally, improvement of fermentation conditions and design of enhanced bioprocesses involving marine actinobacteria and fungi will be considered in view of their efforts to reduce production costs and to achieve high-quality bioactive compounds.

Dr. Fabrizio Beltrametti
Dr. Beatriz Cámara
Dr. Francesca Berini
Guest Editors

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Keywords

  • bioactive molecules
  • secondary metabolites
  • bioactive proteins
  • antibiotic
  • anticancer
  • immunosuppressant
  • antiviral
  • fermentation improvement
  • bioprocesses
  • bioreactors

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Published Papers (6 papers)

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Research

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12 pages, 2871 KiB  
Article
Secondary Metabolites and Biosynthetic Gene Clusters Analysis of Deep-Sea Hydrothermal Vent-Derived Streptomyces sp. SCSIO ZS0520
by Huaran Zhang, Yingying Chen, Yanqing Li, Yongxiang Song, Junying Ma and Jianhua Ju
Mar. Drugs 2022, 20(6), 393; https://doi.org/10.3390/md20060393 - 14 Jun 2022
Cited by 6 | Viewed by 3213
Abstract
Streptomyces sp. SCSIO ZS0520 is a deep-sea hydrothermal vent-derived actinomycete. Our previous metabolism investigation showed that Streptomyces sp. SCSIO ZS0520 is a producer of cytotoxic actinopyrones. Here, another four types of secondary metabolites were identified, including six salinomycin isomers (27 [...] Read more.
Streptomyces sp. SCSIO ZS0520 is a deep-sea hydrothermal vent-derived actinomycete. Our previous metabolism investigation showed that Streptomyces sp. SCSIO ZS0520 is a producer of cytotoxic actinopyrones. Here, another four types of secondary metabolites were identified, including six salinomycin isomers (27), the macrolide elaiophylin (8), the triterpene N-acetyl-aminobacteriohopanetriol (9), and the pyrone minipyrone (10). Among them, compounds 26 and 10 are new compounds. To understand the biosynthetic pathway of these compounds, a bioinformatic analysis of the whole genome was carried out, which identified 34 secondary metabolite biosynthetic gene clusters. Next, the biosynthetic pathways responsive to four types of products were deduced on the basis of gene function predictions and structure information. Taken together, these findings prove the metabolite potential of ZS0520 and lay the foundations to solve the remaining biosynthetic issues in four types of marine natural products. Full article
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13 pages, 2739 KiB  
Article
Diverse Secondary Metabolites from the Coral-Derived Fungus Aspergillus hiratsukae SCSIO 5Bn1003
by Qi Zeng, Yuchan Chen, Junfeng Wang, Xuefeng Shi, Yihao Che, Xiayu Chen, Weimao Zhong, Weimin Zhang, Xiaoyi Wei, Fazuo Wang and Si Zhang
Mar. Drugs 2022, 20(2), 150; https://doi.org/10.3390/md20020150 - 18 Feb 2022
Cited by 7 | Viewed by 3010
Abstract
Three new metabolites, including a cyclic tetrapeptide asperhiratide (1), an ecdysteroid derivative asperhiratine (2), and a sesquiterpene lactone asperhiratone (3), were isolated and identified from the soft coral-derived fungus Aspergillus hiratsukae SCSIO 5Bn1003, together with [...] Read more.
Three new metabolites, including a cyclic tetrapeptide asperhiratide (1), an ecdysteroid derivative asperhiratine (2), and a sesquiterpene lactone asperhiratone (3), were isolated and identified from the soft coral-derived fungus Aspergillus hiratsukae SCSIO 5Bn1003, together with 10 known compounds. Their structures were elucidated via spectroscopic analysis, X-ray diffraction analysis, and electronic circular dichroism calculations. In addition, the absolute configuration of 1 was determined by Marfey’s technique and an analysis of the acid hydrolysates using a chiral phase HPLC column. Among all the compounds, 6 and 8 showed medium cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), with IC50 values ranging from 31.03 ± 3.04 to 50.25 ± 0.54 µM. Meanwhile, they strongly inhibited α-glucosidase activities, with IC50 values of 35.73 ± 3.94 and 22.00 ± 2.45 µM, which were close to and even stronger than the positive control acarbose (IC50 = 32.92 ± 1.03 µM). Compounds 68 showed significant antibacterial activities against Bacillus subtilis, with MIC values of 10.26 ± 0.76 µM, 17.00 ± 1.25 µM, and 5.30 ± 0.29 µM, respectively. Compounds 9 and 12 exhibited potent radical scavenging activities against DPPH, with IC50 values of 12.23 ± 0.78 µM and 7.38 ± 1.16 µM. In addition, asperhiratide (1) was evaluated for anti-angiogenic activities in the in vivo zebrafish model, which showed a weak inhibitory effect on intersegmental vessel (ISV) formation. Full article
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13 pages, 2183 KiB  
Article
Inhibitory Effects of Nitrogenous Metabolites from a Marine-Derived Streptomyces bacillaris on Isocitrate Lyase of Candida albicans
by Beomkoo Chung, Ji-Yeon Hwang, Sung Chul Park, Oh-Seok Kwon, Eunji Cho, Jayho Lee, Hyi-Seung Lee, Dong-Chan Oh, Jongheon Shin and Ki-Bong Oh
Mar. Drugs 2022, 20(2), 138; https://doi.org/10.3390/md20020138 - 13 Feb 2022
Cited by 7 | Viewed by 2999
Abstract
Two nitrogenous metabolites, bacillimide (1) and bacillapyrrole (2), were isolated from the culture broth of the marine-derived actinomycete Streptomyces bacillaris. Based on the results of combined spectroscopic and chemical analyses, the structure of bacillimide (1) was [...] Read more.
Two nitrogenous metabolites, bacillimide (1) and bacillapyrrole (2), were isolated from the culture broth of the marine-derived actinomycete Streptomyces bacillaris. Based on the results of combined spectroscopic and chemical analyses, the structure of bacillimide (1) was determined to be a new cyclopenta[c]pyrrole-1,3-dione bearing a methylsulfide group, while the previously reported bacillapyrrole (2) was fully characterized for the first time as a pyrrole-carboxamide bearing an alkyl sulfoxide side chain. Bacillimide (1) and bacillapyrrole (2) exerted moderate (IC50 = 44.24 μM) and weak (IC50 = 190.45 μM) inhibitory effects on Candida albicans isocitrate lyase, respectively. Based on the growth phenotype using icl-deletion mutants and icl expression analyses, we determined that bacillimide (1) inhibits the transcriptional level of icl in C. albicans under C2-carbon-utilizing conditions. Full article
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10 pages, 2028 KiB  
Article
New Trichothecenes Isolated from the Marine Algicolous Fungus Trichoderma brevicompactum
by Safwan Safwan, Shih-Wei Wang, George Hsiao, Sui-Wen Hsiao, Su-Jung Hsu, Tzong-Huei Lee and Ching-Kuo Lee
Mar. Drugs 2022, 20(2), 80; https://doi.org/10.3390/md20020080 - 18 Jan 2022
Cited by 10 | Viewed by 2548
Abstract
Eight trichothecenes, including four new compounds 14 and four known entities 58, together with one known cyclonerane (9) were isolated from the solid-state fermentation of Trichoderma brevicompactum NTU439 isolated from the marine alga Mastophora rosea [...] Read more.
Eight trichothecenes, including four new compounds 14 and four known entities 58, together with one known cyclonerane (9) were isolated from the solid-state fermentation of Trichoderma brevicompactum NTU439 isolated from the marine alga Mastophora rosea. The structures of 19 were determined by 1D/2D NMR (nuclear magnetic resonance), MS (mass spectrometry), and IR (infrared spectroscopy) spectroscopic data. All of the compounds were evaluated for cytotoxic activity against HCT-116, PC-3, and SK-Hep-1 cancer cells by the SRB assay, and compound 8 showed promising cytotoxic activity against all three cancer cell lines with the IC50 values of 3.3 ± 0.3, 5.3 ± 0.3, and 1.8 ± 0.8 μM, respectively. Compounds 12, 46, and 78 potently inhibited LPS-induced NO production, and compounds 5 and 8 showed markedly inhibited gelatinolysis of MMP-9 in S1 protein-stimulated THP-1 monocytes. Full article
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13 pages, 3151 KiB  
Article
Influence of Cultivation Conditions on the Sioxanthin Content and Antioxidative Protection Effect of a Crude Extract from the Vegetative Mycelium of Salinispora tropica
by Zuzana Jezkova, Vera Schulzova, Ivana Krizova, Marcel Karabin and Tomas Branyik
Mar. Drugs 2021, 19(9), 509; https://doi.org/10.3390/md19090509 - 8 Sep 2021
Cited by 1 | Viewed by 2432
Abstract
Due to their bioavailability, glycosylated carotenoids may have interesting biological effects. Sioxanthin, as a representative of this type of carotenoid, has been identified in marine actinomycetes of the genus Salinispora. This study evaluates, for the first time, the effect of cultivation temperature [...] Read more.
Due to their bioavailability, glycosylated carotenoids may have interesting biological effects. Sioxanthin, as a representative of this type of carotenoid, has been identified in marine actinomycetes of the genus Salinispora. This study evaluates, for the first time, the effect of cultivation temperature (T) and light intensity (LI) on the total cellular carotenoid content (TC), antioxidant activity (AA) and sioxanthin content (SX) of a crude extract (CE) from Salinispora tropica biomass in its vegetative state. Treatment-related differences in TC and SX values were statistically significantly and positively affected by T and LI, while AA was most significantly affected by T. In the S. tropica CE, TC correlated well (R2 = 0.823) with SX and somewhat less with AA (R2 = 0.777). A correlation between AA and SX was found to be less significant (R2 = 0.731). The most significant protective effect against oxidative stress was identified in the CE extracted from S. tropica biomass grown at the highest T and LI (CE-C), as was demonstrated using LNCaP and KYSE-30 human cell lines. The CE showed no cytotoxicity against LNCaP and KYSE-30 cell lines. Full article
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Review

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23 pages, 4241 KiB  
Review
Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization
by Anne-Sofie De Rop, Jeltien Rombaut, Thomas Willems, Marilyn De Graeve, Lynn Vanhaecke, Paco Hulpiau, Sofie L. De Maeseneire, Maarten L. De Mol and Wim K. Soetaert
Mar. Drugs 2022, 20(1), 6; https://doi.org/10.3390/md20010006 - 22 Dec 2021
Cited by 11 | Viewed by 6821
Abstract
The marine environment is an excellent resource for natural products with therapeutic potential. Its microbial inhabitants, often associated with other marine organisms, are specialized in the synthesis of bioactive secondary metabolites. Similar to their terrestrial counterparts, marine Actinobacteria are a prevalent source of [...] Read more.
The marine environment is an excellent resource for natural products with therapeutic potential. Its microbial inhabitants, often associated with other marine organisms, are specialized in the synthesis of bioactive secondary metabolites. Similar to their terrestrial counterparts, marine Actinobacteria are a prevalent source of these natural products. Here, we discuss 77 newly discovered alkaloids produced by such marine Actinobacteria between 2017 and mid-2021, as well as the strategies employed in their elucidation. While 12 different classes of alkaloids were unraveled, indoles, diketopiperazines, glutarimides, indolizidines, and pyrroles were most dominant. Discoveries were mainly based on experimental approaches where microbial extracts were analyzed in relation to novel compounds. Although such experimental procedures have proven useful in the past, the methodologies need adaptations to limit the chance of compound rediscovery. On the other hand, genome mining provides a different angle for natural product discovery. While the technology is still relatively young compared to experimental screening, significant improvement has been made in recent years. Together with synthetic biology tools, both genome mining and extract screening provide excellent opportunities for continued drug discovery from marine Actinobacteria. Full article
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