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Molecular Genetics and Biosynthesis of Biotechnological Products by Filamentous Fungi and Yeasts

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 2983

Special Issue Editors

Dr. Carlos García-Estrada

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Guest Editor
1. Instituto de Biotecnología de León (INBIOTEC), León, Spain
2. Departamento de Ciencias Biomédicas, Facultad de Veterinaria, Campus de Vegazana, Universidad de León, 24071 León, Spain
Interests: fungal secondary metabolism; molecular biology; biotechnology; genetic engineering; omics
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Juan Francisco Martín

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Guest Editor
Department of Molecular Biology, University of Leon, 24071 León, Spain
Interests: fungal molecular genetics; Streptomyces molecular genetics
Dr. Carlos Barreiro

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Guest Editor
Área de Bioquímica y Biología Molecular, Departamento de Biología Molecular, Universidad de León, 24007 León, Spain
Interests: secondary metabolites; microorganisms; proteomics; plastics; actinobacteria; fungi; carotenoids; steroids; immunosuppressors; antibiotics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Filamentous fungi and yeasts are important eukaryotic organisms from a biotechnological point of view, since they are able to synthesize relevant primary and secondary metabolites (organic acids, antibiotics, immunosuppressants, pigments, mycotoxins, etc.), and are also used as platforms for the production of heterologous and homologous proteins. This Special Issue of the International Journal of Molecular Sciences invites researchers to contribute research articles, reviews and opinions addressing relevant topics in molecular genetics and aspects related to the biosynthesis of primary and secondary metabolites and macromolecules of industrial interest by filamentous fungi and yeasts. These topics can include, but are not limited to, the genetic analysis of biosynthetic gene clusters, the transport of metabolites, regulatory circuits and transcription factors, epigenetic regulation, bioinformatics and genome mining, metabolic engineering and synthetic biology, the isolation and structural elucidation of novel fungal secondary metabolites, protein expression and any other biotechnological applications of these microorganisms.

Dr. Carlos García-Estrada
Prof. Dr. Juan Francisco Martín
Dr. Carlos Barreiro
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • filamentous fungi
  • yeasts
  • eukaryotic organisms
  • primary and secondary metabolites
  • biotechnological products

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Published Papers (4 papers)

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Research

16 pages, 1026 KiB  
Article
Modification of B-Nor Steroids Mediated by Filamentous Fungus Fusarium culmorum: Focus on 15α-Hydroxylase Activity
by Alina Świzdor, Tomasz Janeczko and Anna Panek
Int. J. Mol. Sci. 2024, 25(22), 11913; https://doi.org/10.3390/ijms252211913 - 6 Nov 2024
Viewed by 378
Abstract
The metabolic activities of microorganisms to modify the chemical structures of organic compounds are an effective tool for the production of high-value steroidal drugs or active pharmaceutical ingredients (APIs). The integration of biotransformation into the synthesis of APIs can greatly reduce the number [...] Read more.
The metabolic activities of microorganisms to modify the chemical structures of organic compounds are an effective tool for the production of high-value steroidal drugs or active pharmaceutical ingredients (APIs). The integration of biotransformation into the synthesis of APIs can greatly reduce the number of reaction steps and achieve higher process efficiency, thus enabling their greener production. The current research efforts are focused on either the optimization of existing processes or identification of new potentially useful bioconversions. This study aimed to assess the catalytic abilities of the filamentous fungus Fusarium culmorum AM 282 to transform B-nor analogues (5(6→7)abeo compounds) of steroid hormones: androstenedione (AD), dehydroepiandrosterone (DHEA) and its acetate. Our previous studies have demonstrated that this strain is an active hydroxylating catalyst for many steroidal compounds with diverse structures. The results presented in this work showed that the hydroxylation of B-nor steroids occurred with the regio- and stereoselectivity typical of this strain in relation to the corresponding natural hormones of the standard 6:6 A/B series. After the transformations of B-nor-DHEA and its acetate, 15α-hydroxy-B-nor-DHEA was obtained as the sole product of the reaction, while the transformation of the AD analogue resulted in a mixture of its 15α- and 6α-hydroxy derivatives. A detailed analysis of the transformation course indicated that all the obtained hydroxy derivatives could be the result of the activity of the same enzyme. The presented results may provide a basis for research aimed at understanding the molecular nature of cytochrome P-450 monooxygenase from F. culmorum AM 282 with its ability for 15α-hydroxylation of steroidal compounds. An analysis of the pharmacokinetic and pharmacodynamic properties of the obtained metabolites with cheminformatics tools suggests their potential biological activity. Full article
(This article belongs to the Special Issue Molecular Genetics and Biosynthesis of Biotechnological Products by Filamentous Fungi and Yeasts)
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15 pages, 1803 KiB  
Article
Metabolic Engineering and Process Intensification for Muconic Acid Production Using Saccharomyces cerevisiae
by Sinah Tönjes, Evelien Uitterhaegen, Ilse Palmans, Birthe Ibach, Karel De Winter, Patrick Van Dijck, Wim Soetaert and Paul Vandecruys
Int. J. Mol. Sci. 2024, 25(19), 10245; https://doi.org/10.3390/ijms251910245 - 24 Sep 2024
Viewed by 1037
Abstract
The efficient production of biobased organic acids is crucial to move to a more sustainable and eco-friendly economy, where muconic acid is gaining interest as a versatile platform chemical to produce industrial building blocks, including adipic acid and terephthalic acid. In this study, [...] Read more.
The efficient production of biobased organic acids is crucial to move to a more sustainable and eco-friendly economy, where muconic acid is gaining interest as a versatile platform chemical to produce industrial building blocks, including adipic acid and terephthalic acid. In this study, a Saccharomyces cerevisiae platform strain able to convert glucose and xylose into cis,cis-muconic acid was further engineered to eliminate C2 dependency, improve muconic acid tolerance, enhance production and growth performance, and substantially reduce the side production of the intermediate protocatechuic acid. This was achieved by reintroducing the PDC5 gene and overexpression of QDR3 genes. The improved strain was integrated in low-pH fed-batch fermentations at bioreactor scale with integrated in situ product recovery. By adding a biocompatible organic phase consisting of CYTOP 503 and canola oil to the process, a continuous extraction of muconic acid was achieved, resulting in significant alleviation of product inhibition. Through this, the muconic acid titer and peak productivity were improved by 300% and 185%, respectively, reaching 9.3 g/L and 0.100 g/L/h in the in situ product recovery process as compared to 3.1 g/L and 0.054 g/L/h in the control process without ISPR. Full article
(This article belongs to the Special Issue Molecular Genetics and Biosynthesis of Biotechnological Products by Filamentous Fungi and Yeasts)
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22 pages, 1741 KiB  
Article
Energy Metabolism Enhance Perylenequinone Biosynthesis in Shiraia sp. Slf14 through Promoting Mitochondrial ROS Accumulation
by Xueyi Wu, Xuan Meng, Yiwen Xiao, Huilin Yang, Zhibin Zhang and Du Zhu
Int. J. Mol. Sci. 2024, 25(18), 10113; https://doi.org/10.3390/ijms251810113 - 20 Sep 2024
Viewed by 543
Abstract
Perylenequinones (PQs) are important natural compounds that have been extensively utilized in recent years as agents for antimicrobial, anticancer, and antiviral photodynamic therapies. In this study, we investigated the molecular mechanisms regulating PQ biosynthesis by comparing Shiraia sp. Slf14 with its low PQ [...] Read more.
Perylenequinones (PQs) are important natural compounds that have been extensively utilized in recent years as agents for antimicrobial, anticancer, and antiviral photodynamic therapies. In this study, we investigated the molecular mechanisms regulating PQ biosynthesis by comparing Shiraia sp. Slf14 with its low PQ titer mutant, Slf14(w). The results indicated that the strain Slf14 exhibited a higher PQ yield, a more vigorous energy metabolism, and a more pronounced oxidation state compared to Slf14(w). Transcriptome analysis consistently revealed that the differences in gene expression between Slf14 and Slf14(w) are primarily associated with genes involved in redox processes and energy metabolism. Additionally, reactive oxygen species (ROS) were shown to play a crucial role in promoting PQ synthesis, as evidenced by the application of ROS-related inhibitors and promoters. Further results demonstrated that mitochondria are significant sources of ROS, which effectively regulate PQ biosynthesis in Shiraia sp. Slf14. In summary, this research revealed a noteworthy finding: the higher energy metabolism of the strain Slf14 is associated with increased intracellular ROS accumulation, which in turn triggers the activation and expression of gene clusters responsible for PQ synthesis. Full article
(This article belongs to the Special Issue Molecular Genetics and Biosynthesis of Biotechnological Products by Filamentous Fungi and Yeasts)
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21 pages, 7715 KiB  
Article
Kinetics of Riboflavin Production by Hyphopichia wangnamkhiaoensis under Varying Nutritional Conditions
by Raziel Arturo Jiménez-Nava, Griselda Ma. Chávez-Camarillo and Eliseo Cristiani-Urbina
Int. J. Mol. Sci. 2024, 25(17), 9430; https://doi.org/10.3390/ijms25179430 - 30 Aug 2024
Viewed by 687
Abstract
Riboflavin, an essential vitamin for humans, is extensively used in various industries, with its global demand being met through fermentative processes. Hyphopichia wangnamkhiaoensis is a novel dimorphic yeast species capable of producing riboflavin. However, the nutritional factors affecting riboflavin production in this yeast [...] Read more.
Riboflavin, an essential vitamin for humans, is extensively used in various industries, with its global demand being met through fermentative processes. Hyphopichia wangnamkhiaoensis is a novel dimorphic yeast species capable of producing riboflavin. However, the nutritional factors affecting riboflavin production in this yeast species remain unknown. Therefore, we conducted a kinetic study on the effects of various nutritional factors—carbon and energy sources, nitrogen sources, vitamins, and amino acids—on batch riboflavin production by H. wangnamkhiaoensis. Batch experiments were performed in a bubble column bioreactor to evaluate cell growth, substrate consumption, and riboflavin production. The highest riboflavin production was obtained when the yeast growth medium was supplemented with glucose, ammonium sulfate, biotin, and glycine. Using these chemical components, along with the mineral salts from Castañeda-Agullo’s culture medium, we formulated a novel, low-cost, and effective culture medium (the RGE medium) for riboflavin production by H. wangnamkhiaoensis. This medium resulted in the highest levels of riboflavin production and volumetric productivity, reaching 16.68 mg/L and 0.713 mg/L·h, respectively, within 21 h of incubation. These findings suggest that H. wangnamkhiaoensis, with its shorter incubation time, could improve the efficiency and cost-effectiveness of industrial riboflavin production, paving the way for more sustainable production methods. Full article
(This article belongs to the Special Issue Molecular Genetics and Biosynthesis of Biotechnological Products by Filamentous Fungi and Yeasts)
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