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Recent Advances in Fungal Secondary Metabolism
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Recent Advances in Fungal Secondary Metabolism

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Cell Biology, Metabolism and Physiology".

Deadline for manuscript submissions: closed (30 August 2023) | Viewed by 10802

Special Issue Editors

Dr. Carlos García-Estrada

E-Mail Website
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
Dr. Inmaculada Vaca

E-Mail Website
Guest Editor
Departamento de Química, Facultad de Ciencias, Universidad de Chile, Santiago, ‎Chile
Interests: fungal secondary metabolism; natural products; fungi from Antarctica
Special Issues, Collections and Topics in MDPI journals
Dr. Renato Chávez

E-Mail Website
Guest Editor
Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile
Interests: fungal secondary metabolism; fungal biology; fungi from Antarctica
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The kingdom Fungi includes a diverse group of eukaryotic organisms able to produce a vast array of chemically diverse natural products, known as secondary metabolites, which are important from the biotechnological point of view and include antibiotics, immunosuppressants, pigments, mycotoxins, etc.

This Special Issue of Journal of Fungi invites researchers to contribute research articles, reviews, and opinions addressing relevant topics in fungal secondary metabolism including, but not limited to, the genetic analysis of biosynthetic gene clusters, intra- and extracellular transport of secondary metabolites, regulatory circuits and transcription factors, epigenetic regulation, bioinformatics and genome mining, metabolic engineering and synthetic biology, isolation and structural elucidation of novel fungal secondary metabolites, bioactivity assessment of pure natural products from fungi, and fungal metabolomics.

Dr. Carlos García-Estrada
Dr. Inmaculada Vaca
Dr. Renato Chávez
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. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • natural products
  • fungal secondary metabolism
  • biosynthetic gene clusters (BGCs)
  • regulatory mechanisms
  • fungal biotechnology
  • metabolomics

Published Papers (6 papers)

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Research

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18 pages, 4296 KiB  
Article
Metabolic Changes and Antioxidant Response in Ustilago maydis Grown in Acetate
by Lucero Romero-Aguilar, Katia Daniela Hernández-Morfín, Guadalupe Guerra-Sánchez and Juan Pablo Pardo
J. Fungi 2023, 9(7), 749; https://doi.org/10.3390/jof9070749 - 14 Jul 2023
Cited by 1 | Viewed by 1156
Abstract
Ustilago maydis is an important model to study intermediary and mitochondrial metabolism, among other processes. U. maydis can grow, at very different rates, on glucose, lactate, glycerol, and ethanol as carbon sources. Under nitrogen starvation and glucose as the only carbon source, this [...] Read more.
Ustilago maydis is an important model to study intermediary and mitochondrial metabolism, among other processes. U. maydis can grow, at very different rates, on glucose, lactate, glycerol, and ethanol as carbon sources. Under nitrogen starvation and glucose as the only carbon source, this fungus synthesizes and accumulates neutral lipids in the form of lipid droplets (LD). In this work, we studied the accumulation of triacylglycerols in cells cultured in a medium containing acetate, a direct precursor of the acetyl-CoA required for the synthesis of fatty acids. The metabolic adaptation of cells to acetate was studied by measuring the activities of key enzymes involved in glycolysis, gluconeogenesis, and the pentose phosphate pathways. Since growth on acetate induces oxidative stress, the activities of some antioxidant enzymes were also assayed. The results show that cells grown in acetate plus nitrate did not increase the amount of LD, but increased the activities of glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase, suggesting a higher production of reactive oxygen species in cells growing in acetate. The phosphofructokinase-1 (PFK1) was the enzyme with the lowest specific activity in the glycolytic pathway, suggesting that PFK1 controls the flux of glycolysis. As expected, the activity of the phosphoenolpyruvate carboxykinase, a gluconeogenic enzyme, was present only in the acetate condition. In summary, in the presence of acetate as the only carbon source, U. maydis synthesized fatty acids, which were directed into the production of phospholipids and neutral lipids for biomass generation, but without any excessive accumulation of LD. Full article
(This article belongs to the Special Issue Recent Advances in Fungal Secondary Metabolism)
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18 pages, 3747 KiB  
Article
Mutational Analysis of Aspergillus fumigatus Volatile Oxylipins in a Drosophila Eclosion Assay
by Hadeel S. Almaliki, Mengyao Niu, Nancy P. Keller, Guohua Yin and Joan W. Bennett
J. Fungi 2023, 9(4), 402; https://doi.org/10.3390/jof9040402 - 24 Mar 2023
Cited by 2 | Viewed by 1594
Abstract
Aspergillus fumigatus is a ubiquitous opportunistic pathogen. We have previously reported that volatile organic compounds (VOCs) produced by A. fumigatus cause delays in metamorphosis, morphological abnormalities, and death in a Drosophila melanogaster eclosion model. Here, we developed A. fumigatus deletion mutants with [...] Read more.
Aspergillus fumigatus is a ubiquitous opportunistic pathogen. We have previously reported that volatile organic compounds (VOCs) produced by A. fumigatus cause delays in metamorphosis, morphological abnormalities, and death in a Drosophila melanogaster eclosion model. Here, we developed A. fumigatus deletion mutants with blocked oxylipin biosynthesis pathways (∆ppoABC) and then exposed the third instar larvae of D. melanogaster to a shared atmosphere with either A. fumigatus wild-type or oxylipin mutant cultures for 15 days. Fly larvae exposed to VOCs from wild-type A. fumigatus strains exhibited delays in metamorphosis and toxicity, while larvae exposed to VOCs from the ∆ppoABC mutant displayed fewer morphogenic delays and higher eclosion rates than the controls. In general, when fungi were pre-grown at 37 °C, the effects of the VOCs they produced were more pronounced than when they were pre-grown at 25 °C. GC–MS analysis revealed that the wild-type A. fumigatus Af293 produced more abundant VOCs at higher concentrations than the oxylipin-deficient strain Af293∆ppoABC did. The major VOCs detected from wild-type Af293 and its triple mutant included isopentyl alcohol, isobutyl alcohol, 2-methylbutanal, acetoin, and 1-octen-3-ol. Unexpectedly, compared to wild-type flies, the eclosion tests yielded far fewer differences in metamorphosis or viability when flies with immune-deficient genotypes were exposed to VOCs from either wild-type or ∆ppoABC oxylipin mutants. In particular, the toxigenic effects of Aspergillus VOCs were not observed in mutant flies deficient in the Toll (spz6) pathway. These data indicate that the innate immune system of Drosophila mediates the toxicity of fungal volatiles, especially via the Toll pathway. Full article
(This article belongs to the Special Issue Recent Advances in Fungal Secondary Metabolism)
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Review

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19 pages, 1351 KiB  
Review
Secondary Metabolites from Fungi Microsphaeropsis spp.: Chemistry and Bioactivities
by Guodong Song, Zhibin Zhang, Xuenan Niu and Du Zhu
J. Fungi 2023, 9(11), 1093; https://doi.org/10.3390/jof9111093 - 09 Nov 2023
Viewed by 967
Abstract
Microsphaeropsis, taxonomically classified within the kingdom fungi, phylum Ascomycota, subphylum Deuteromycotina, class Coelomycetes, order Sphaeropsidales, and family Sphaeropsidaceae, exhibit a ubiquitous distribution across various geographical regions. These fungi are known for their production of secondary metabolites, characterized by both structural novelty and [...] Read more.
Microsphaeropsis, taxonomically classified within the kingdom fungi, phylum Ascomycota, subphylum Deuteromycotina, class Coelomycetes, order Sphaeropsidales, and family Sphaeropsidaceae, exhibit a ubiquitous distribution across various geographical regions. These fungi are known for their production of secondary metabolites, characterized by both structural novelty and potent biological activity. Consequently, they represent a significant reservoir for the advancement of novel pharmaceuticals. In this paper, a systematic review was present, marking the analysis of secondary metabolites synthesized by Microsphaeropsis reported between 1980 and 2023. A total of 112 compounds, comprising polyketones, macrolides, terpenoids, and nitrogen-containing compounds, were reported from Microsphaeropsis. Remarkably, among these compounds, 49 are novel discoveries, marking a significant contribution to the field. A concise summary of their diverse biological activities was provided, including antibacterial, antitumor, and antiviral properties and other bioactivities. This analysis stands as a valuable reference, poised to guide further investigations into the active natural products derived from Microsphaeropsis and their potential contributions to the development of medicinal resources. Full article
(This article belongs to the Special Issue Recent Advances in Fungal Secondary Metabolism)
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19 pages, 1014 KiB  
Review
Genetic and Environmental Factors Influencing the Production of Select Fungal Colorants: Challenges and Opportunities in Industrial Applications
by Lan Lin, Tong Zhang and Jianping Xu
J. Fungi 2023, 9(5), 585; https://doi.org/10.3390/jof9050585 - 18 May 2023
Cited by 1 | Viewed by 1374
Abstract
Natural colorants, mostly of plant and fungal origins, offer advantages over chemically synthetic colorants in terms of alleviating environmental pollution and promoting human health. The market value of natural colorants has been increasing significantly across the globe. Due to the ease of artificially [...] Read more.
Natural colorants, mostly of plant and fungal origins, offer advantages over chemically synthetic colorants in terms of alleviating environmental pollution and promoting human health. The market value of natural colorants has been increasing significantly across the globe. Due to the ease of artificially culturing most fungi in the laboratory and in industrial settings, fungi have emerged as the organisms of choice for producing many natural colorants. Indeed, there is a wide variety of colorful fungi and a diversity in the structure and bioactivity of fungal colorants. Such broad diversities have spurred significant research efforts in fungi to search for natural alternatives to synthetic colorants. Here, we review recent research on the genetic and environmental factors influencing the production of three major types of natural fungal colorants: carotenoids, melanins, and polyketide-derived colorants. We highlight how molecular genetic studies and environmental condition manipulations are helping to overcome some of the challenges associated with value-added and large-scale productions of these colorants. We finish by discussing potential future trends, including synthetic biology approaches, in the commercial production of fungal colorants. Full article
(This article belongs to the Special Issue Recent Advances in Fungal Secondary Metabolism)
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28 pages, 4424 KiB  
Review
Secondary Metabolites Produced by the Blue-Cheese Ripening Mold Penicillium roqueforti; Biosynthesis and Regulation Mechanisms
by Renato Chávez, Inmaculada Vaca and Carlos García-Estrada
J. Fungi 2023, 9(4), 459; https://doi.org/10.3390/jof9040459 - 10 Apr 2023
Cited by 2 | Viewed by 2531
Abstract
Filamentous fungi are an important source of natural products. The mold Penicillium roqueforti, which is well-known for being responsible for the characteristic texture, blue-green spots, and aroma of the so-called blue-veined cheeses (French Bleu, Roquefort, Gorgonzola, Stilton, Cabrales, and Valdeón, among others), [...] Read more.
Filamentous fungi are an important source of natural products. The mold Penicillium roqueforti, which is well-known for being responsible for the characteristic texture, blue-green spots, and aroma of the so-called blue-veined cheeses (French Bleu, Roquefort, Gorgonzola, Stilton, Cabrales, and Valdeón, among others), is able to synthesize different secondary metabolites, including andrastins and mycophenolic acid, as well as several mycotoxins, such as Roquefortines C and D, PR-toxin and eremofortins, Isofumigaclavines A and B, festuclavine, and Annullatins D and F. This review provides a detailed description of the biosynthetic gene clusters and pathways of the main secondary metabolites produced by P. roqueforti, as well as an overview of the regulatory mechanisms controlling secondary metabolism in this filamentous fungus. Full article
(This article belongs to the Special Issue Recent Advances in Fungal Secondary Metabolism)
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16 pages, 1946 KiB  
Review
Biotechnological Fungal Platforms for the Production of Biosynthetic Cannabinoids
by Katarina Kosalková, Carlos Barreiro, Isabel-Clara Sánchez-Orejas, Laura Cueto and Carlos García-Estrada
J. Fungi 2023, 9(2), 234; https://doi.org/10.3390/jof9020234 - 10 Feb 2023
Viewed by 2528
Abstract
Cannabinoids are bioactive meroterpenoids comprising prenylated polyketide molecules that can modulate a wide range of physiological processes. Cannabinoids have been shown to possess various medical/therapeutic effects, such as anti-convulsive, anti-anxiety, anti-psychotic, antinausea, and anti-microbial properties. The increasing interest in their beneficial effects and [...] Read more.
Cannabinoids are bioactive meroterpenoids comprising prenylated polyketide molecules that can modulate a wide range of physiological processes. Cannabinoids have been shown to possess various medical/therapeutic effects, such as anti-convulsive, anti-anxiety, anti-psychotic, antinausea, and anti-microbial properties. The increasing interest in their beneficial effects and application as clinically useful drugs has promoted the development of heterologous biosynthetic platforms for the industrial production of these compounds. This approach can help circumvent the drawbacks associated with extraction from naturally occurring plants or chemical synthesis. In this review, we provide an overview of the fungal platforms developed by genetic engineering for the biosynthetic production of cannabinoids. Different yeast species, such as Komagataella phaffii (formerly P. pastoris) and Saccharomyces cerevisiae, have been genetically modified to include the cannabinoid biosynthetic pathway and to improve metabolic fluxes in order to increase cannabinoid titers. In addition, we engineered the filamentous fungus Penicillium chrysogenum for the first time as a host microorganism for the production of Δ9-tetrahydrocannabinolic acid from intermediates (cannabigerolic acid and olivetolic acid), thereby showing the potential of filamentous fungi as alternative platforms for cannabinoid biosynthesis upon optimization. Full article
(This article belongs to the Special Issue Recent Advances in Fungal Secondary Metabolism)
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