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Special Issue "Evolutionary/Phylogenetic Studies of Mycotoxin Biosynthetic Pathways 2013"

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A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Mycotoxins".

Deadline for manuscript submissions: closed (31 January 2013)

Special Issue Editors

Guest Editor
Dr. Charles W. Bacon (Website)

Toxicology and Mycotoxin Research, Russell Research Center, 950 College Station Road, Athens, GA 30604, USA
Fax: +1 706 546 3116
Interests: regulation and biosynthesis of mycotoxins; fungal endophyte-grass relationships; bacterial endophytes, and the coevolution of secondary products; primarily mycotoxins, with grasses and other plants, as an adaptive strategy for mutualistic associations
Guest Editor
Dr. Scott Gold (Website)

Toxicology and Mycotoxin Research, Russell Research Center, 950 College Station Road, Athens, GA 30604, USA

Special Issue Information

Dear Colleagues,

Over five decades ago the turkey X disease demonstrated the devastating effects that consumption of feed contaminated by a fungus and its metabolite can have on poultry. The fungus was identified as Aspergillus flavus and its toxins, the aflatoxins. We now know that the aflatoxins are toxic not only to turkeys but also to other poultry, livestock and humankind. This one mycotoxin served as a world-wide impetus for studies on fungal toxins with the major objective of control and prevention. From this initiative we are now aware of several very toxic fungal metabolites of which most have very wide spectrum of activity on animals and some also affect plants. Since the discovery of aflatoxins, mycotoxicologists have studied the phenomenon of secondary metabolism from fungal physiological, biochemical and plant pathological perspectives, which developed into sophisticated genetic approaches, and now to molecular analysis evolving into our present day series of genomics, proteomics and metabolomic investigations, which in themselves are grouped into the neologism “omics” with the ultimate desire of leading to biological studies at an interactive level. In this issue we have assembled a group of world-class contributors studying the phenomenon of mycotoxin and secondary metabolisms in fungi leading to the accumulation of various toxins in our food and feed supplies while providing some insights into the phylogeny and evolutionary consequences of the synthesis of mycotoxins and their varied pathways. In some studies the evidence is clear for a defensive role and a survival strategy along with clear evolutionary tendencies among producing species. In several instances these studies highlight and or review omics investigations at our current level of understanding as well as their impact on the basic mandate of control of these disastrous metabolites and or their producing organisms.

Dr. Charles W. Bacon
Dr. Scott Gold
Guest Editors

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on theInstructions for Authors page. Toxins 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 800 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • aspergillus
  • fusarium
  • fungal toxins
  • fungal secondary metabolites
  • fungal endophytes
  • metabolomics
  • mycotoxins
  • omics

Related Special Issue

Published Papers (7 papers)

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Research

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Open AccessArticle Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli
Toxins 2013, 5(8), 1422-1446; doi:10.3390/toxins5081422
Received: 5 June 2013 / Revised: 22 July 2013 / Accepted: 2 August 2013 / Published: 14 August 2013
Cited by 5 | PDF Full-text (4365 KB) | HTML Full-text | XML Full-text
Abstract
The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of [...] Read more.
The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse). This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis. Full article
Open AccessArticle Currencies of Mutualisms: Sources of Alkaloid Genes in Vertically Transmitted Epichloae
Toxins 2013, 5(6), 1064-1088; doi:10.3390/toxins5061064
Received: 1 April 2013 / Revised: 17 May 2013 / Accepted: 29 May 2013 / Published: 6 June 2013
Cited by 28 | PDF Full-text (384 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The epichloae (Epichloë and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae). Most epichloae are vertically transmitted in seeds (endophytes), and most produce alkaloids that attack nervous systems of [...] Read more.
The epichloae (Epichloë and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae). Most epichloae are vertically transmitted in seeds (endophytes), and most produce alkaloids that attack nervous systems of potential herbivores. These protective metabolites include ergot alkaloids and indole-diterpenes (tremorgens), which are active in vertebrate systems, and lolines and peramine, which are more specific against invertebrates. Several Epichloë species have been described which are sexual and capable of horizontal transmission, and most are vertically transmissible also. Asexual epichloae are mainly or exclusively vertically transmitted, and many are interspecific hybrids with genomic contributions from two or three ancestral Epichloë species. Here we employ genome-scale analyses to investigate the origins of biosynthesis gene clusters for ergot alkaloids (EAS), indole-diterpenes (IDT), and lolines (LOL) in 12 hybrid species. In each hybrid, the alkaloid-gene and housekeeping-gene relationships were congruent. Interestingly, hybrids frequently had alkaloid clusters that were rare in their sexual ancestors. Also, in those hybrids that had multiple EAS, IDT or LOL clusters, one cluster lacked some genes, usually for late pathway steps. Possible implications of these findings for the alkaloid profiles and endophyte ecology are discussed. Full article
Figures

Open AccessArticle Phylogenetic Study of Polyketide Synthases and Nonribosomal Peptide Synthetases Involved in the Biosynthesis of Mycotoxins
Toxins 2013, 5(4), 717-742; doi:10.3390/toxins5040717
Received: 27 February 2013 / Revised: 22 March 2013 / Accepted: 10 April 2013 / Published: 19 April 2013
Cited by 13 | PDF Full-text (1005 KB) | HTML Full-text | XML Full-text
Abstract
Polyketide synthase (PKSs) and nonribosomal peptide synthetase (NRPSs) are large multimodular enzymes involved in biosynthesis of polyketide and peptide toxins produced by fungi. Furthermore, hybrid enzymes, in which a reducing PKS region is fused to a single NRPS module, are also responsible [...] Read more.
Polyketide synthase (PKSs) and nonribosomal peptide synthetase (NRPSs) are large multimodular enzymes involved in biosynthesis of polyketide and peptide toxins produced by fungi. Furthermore, hybrid enzymes, in which a reducing PKS region is fused to a single NRPS module, are also responsible of the synthesis of peptide-polyketide metabolites in fungi. The genes encoding for PKSs and NRPSs have been exposed to complex evolutionary mechanisms, which have determined the great number and diversity of metabolites. In this study, we considered the most important polyketide and peptide mycotoxins and, for the first time, a phylogenetic analysis of both PKSs and NRPSs involved in their biosynthesis was assessed using two domains for each enzyme: β-ketosynthase (KS) and acyl-transferase (AT) for PKSs; adenylation (A) and condensation (C) for NRPSs. The analysis of both KS and AT domains confirmed the differentiation of the three classes of highly, partially and non-reducing PKSs. Hybrid PKS-NRPSs involved in mycotoxins biosynthesis grouped together in the phylogenetic trees of all the domains analyzed. For most mycotoxins, the corresponding biosynthetic enzymes from distinct fungal species grouped together, except for PKS and NRPS involved in ochratoxin A biosynthesis, for which an unlike process of evolution could be hypothesized in different species. Full article
Open AccessArticle Diversity of Pea-Associated F. proliferatum and F. verticillioides Populations Revealed by FUM1 Sequence Analysis and Fumonisin Biosynthesis
Toxins 2013, 5(3), 488-503; doi:10.3390/toxins5030488
Received: 2 January 2013 / Revised: 25 January 2013 / Accepted: 22 February 2013 / Published: 7 March 2013
Cited by 11 | PDF Full-text (257 KB) | HTML Full-text | XML Full-text
Abstract
Fusarium proliferatum and F. verticillioides are considered as minor pathogens of pea (Pisum sativum L.). Both species can survive in seed material without visible disease symptoms, but still contaminating it with fumonisins. Two populations of pea-derived F. proliferatum and F. verticillioides [...] Read more.
Fusarium proliferatum and F. verticillioides are considered as minor pathogens of pea (Pisum sativum L.). Both species can survive in seed material without visible disease symptoms, but still contaminating it with fumonisins. Two populations of pea-derived F. proliferatum and F. verticillioides strains were subjected to FUM1 sequence divergence analysis, forming a distinct group when compared to the collection strains originating from different host species. Furthermore, the mycotoxigenic abilities of those strains were evaluated on the basis of in planta and in vitro fumonisin biosynthesis. No differences were observed in fumonisin B (FB) levels measured in pea seeds (maximum level reached 1.5 μg g−1); however, in rice cultures, the majority of F. proliferatum genotypes produced higher amounts of FB1–FB3 than F. verticillioides strains. Full article
Open AccessArticle Partial Reconstruction of the Ergot Alkaloid Pathway by Heterologous Gene Expression in Aspergillus nidulans
Toxins 2013, 5(2), 445-455; doi:10.3390/toxins5020445
Received: 23 January 2013 / Revised: 8 February 2013 / Accepted: 17 February 2013 / Published: 22 February 2013
Cited by 18 | PDF Full-text (1079 KB) | HTML Full-text | XML Full-text
Abstract
Ergot alkaloids are pharmaceutically and agriculturally important secondary metabolites produced by several species of fungi. Ergot alkaloid pathways vary among different fungal lineages, but the pathway intermediate chanoclavine-I is evolutionarily conserved among ergot alkaloid producers. At least four genes, dmaW, easF [...] Read more.
Ergot alkaloids are pharmaceutically and agriculturally important secondary metabolites produced by several species of fungi. Ergot alkaloid pathways vary among different fungal lineages, but the pathway intermediate chanoclavine-I is evolutionarily conserved among ergot alkaloid producers. At least four genes, dmaW, easF, easE, and easC, are necessary for pathway steps prior to chanoclavine-I; however, the sufficiency of these genes for chanoclavine-I synthesis has not been established. A fragment of genomic DNA containing dmaW, easF, easE, and easC was amplified from the human-pathogenic, ergot alkaloid-producing fungus Aspergillus fumigatus and transformed into Aspergillus nidulans, a model fungus that does not contain any of the ergot alkaloid synthesis genes. HPLC and LC-MS analyses demonstrated that transformed A. nidulans strains produced chanoclavine-I and an earlier pathway intermediate. Aspergillus nidulans transformants containing dmaW, easF, and either easE or easC did not produce chanoclavine-I but did produce an early pathway intermediate and, in the case of the easC transformant, an additional ergot alkaloid-like compound. We conclude that dmaW, easF, easE, and easC are sufficient for the synthesis of chanoclavine-I in A. nidulans and expressing ergot alkaloid pathway genes in A. nidulans provides a novel approach to understanding the early steps in ergot alkaloid synthesis. Full article

Review

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Open AccessReview Towards Systems Biology of Mycotoxin Regulation
Toxins 2013, 5(4), 675-682; doi:10.3390/toxins5040675
Received: 25 February 2013 / Revised: 22 March 2013 / Accepted: 10 April 2013 / Published: 18 April 2013
Cited by 3 | PDF Full-text (823 KB) | HTML Full-text | XML Full-text
Abstract
Systems biology is a scientific approach that integrates many scientific disciplines to develop a comprehensive understanding of biological phenomena, thus allowing the prediction and accurate simulation of complex biological behaviors. It may be presumptuous to write about toxin regulation at the level [...] Read more.
Systems biology is a scientific approach that integrates many scientific disciplines to develop a comprehensive understanding of biological phenomena, thus allowing the prediction and accurate simulation of complex biological behaviors. It may be presumptuous to write about toxin regulation at the level of systems biology, but the last decade of research is leading us closer than ever to this approach. Past research has delineated multiple levels of regulation in the pathways leading to the biosynthesis of secondary metabolites, including mycotoxins. At the top of this hierarchy, the global or master transcriptional regulators perceive various environmental cues such as climatic conditions, the availability of nutrients, and the developmental stages of the organism. Information accumulated from various inputs is integrated through a complex web of signalling networks to generate the eventual outcome. This review will focus on adapting techniques such as chemical and other genetic tools available in the model system Saccharomyces cerevisiae, to disentangle the various biological networks involved in the biosynthesis of mycotoxins in the Fusarium spp. Full article
Open AccessReview Oxidative Stress-Related Transcription Factors in the Regulation of Secondary Metabolism
Toxins 2013, 5(4), 683-702; doi:10.3390/toxins5040683
Received: 5 March 2013 / Revised: 1 April 2013 / Accepted: 9 April 2013 / Published: 18 April 2013
Cited by 31 | PDF Full-text (970 KB) | HTML Full-text | XML Full-text
Abstract
There is extensive and unequivocal evidence that secondary metabolism in filamentous fungi and plants is associated with oxidative stress. In support of this idea, transcription factors related to oxidative stress response in yeast, plants, and fungi have been shown to participate in [...] Read more.
There is extensive and unequivocal evidence that secondary metabolism in filamentous fungi and plants is associated with oxidative stress. In support of this idea, transcription factors related to oxidative stress response in yeast, plants, and fungi have been shown to participate in controlling secondary metabolism. Aflatoxin biosynthesis, one model of secondary metabolism, has been demonstrated to be triggered and intensified by reactive oxygen species buildup. An oxidative stress-related bZIP transcription factor AtfB is a key player in coordinate expression of antioxidant genes and genes involved in aflatoxin biosynthesis. Recent findings from our laboratory provide strong support for a regulatory network comprised of at least four transcription factors that bind in a highly coordinated and timely manner to promoters of the target genes and regulate their expression. In this review, we will focus on transcription factors involved in co-regulation of aflatoxin biosynthesis with oxidative stress response in aspergilli, and we will discuss the relationship of known oxidative stress-associated transcription factors and secondary metabolism in other organisms. We will also talk about transcription factors that are involved in oxidative stress response, but have not yet been demonstrated to be affiliated with secondary metabolism. The data support the notion that secondary metabolism provides a secondary line of defense in cellular response to oxidative stress. Full article

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