Metabolic Pathway Gene Clusters in Filamentous Fungi

Keller, Nancy P.; Höhn, Thomas

doi:10.1006/fgbi.1997.0970

Cited by 556 publications

(388 citation statements)

References 87 publications

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“…The evolutionary reasons for clustering have been often debated; the explanation that is best supported by experimental data is that clustering facilitates transcriptional coregulation (11). This hypothesis is based on the assumption that the contiguous arrangement of genes cooperating in a metabolic pathway facilitates their coordinated expression.…”

Section: Discussionmentioning

confidence: 99%

Transcription of Genes in the Biosynthetic Pathway for Fumonisin Mycotoxins Is Epigenetically and Differentially Regulated in the Fungal Maize Pathogen Fusarium verticillioides

et al. 2012

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When the fungal pathogen Gibberella moniliformis (anamorph, Fusarium verticillioides) colonizes maize and maize-based products, it produces class B fumonisin (FB) mycotoxins, which are a significant threat to human and animal health. FB biosynthetic enzymes and accessory proteins are encoded by a set of clustered and cotranscribed genes collectively named FUM, whose molecular regulation is beginning to be unraveled by researchers. FB accumulation correlates with the amount of transcripts from the key FUM genes, FUM1, FUM21, and FUM8. In fungi in general, gene expression is often partially controlled at the chromatin level in secondary metabolism; when this is the case, the deacetylation and acetylation (and other posttranslational modifications) of histones are usually crucial in the regulation of transcription. To assess whether epigenetic factors regulate the FB pathway, we monitored FB production and FUM1, FUM21, and FUM8 expression in the presence of a histone deacetylase inhibitor and verified by chromatin immunoprecipitation the relative degree of histone acetylation in the promoter regions of FUM1, FUM21, and FUM8 under FB-inducing and noninducing conditions. Moreover, we generated transgenic F. verticillioides strains expressing GFP under the control of the FUM1 promoter to determine whether its strength under FB-inducing and noninducing conditions was influenced by its location in the genome. Our results indicate a clear and differential role for chromatin remodeling in the regulation of FUM genes. This epigenetic regulation can be attained through the modulation of histone acetylation at the level of the promoter regions of the key biosynthetic genes FUM1 and FUM21, but less so for FUM8.F umonisins are a family of mycotoxins produced by the secondary metabolism (SM) of Fusarium verticillioides (teleomorph, Gibberella moniliformis) and Fusarium proliferatum that contaminate maize and maize-based products. Within the B series of these toxins (FB), FB1, FB2, and FB3 are the ones most frequently found under field conditions and have been linked to various animal and human mycotoxicoses (23). FB are polyketides consisting of a linear 19-or 20-carbon backbone with hydroxyl, methyl, and tricarballylic acid moieties at various positions along the base chain (19). In filamentous Ascomycetes, genes involved in the biosynthesis of toxins (such as aflatoxins and trichothecenes) and of other secondary metabolites are frequently organized into clusters (6). Clustering is not observed for most biosynthetic genes in the SM of higher eukaryotes, with a few exceptions in plants (7,21). In organisms like filamentous fungi, such clustering occurs and is maintained probably because it facilitates horizontal transfer and coordinated transcriptional regulation of the genes therein (29).The FB biosynthetic gene cluster consists of 17 transcriptionally coregulated genes designated FUM1 through FUM3 and FUM6 through FUM21 (with FUM2 and FUM3 later found to be the same as FUM12 and FUM9, respectively) (1,5,18,26). While the func...

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Section: Discussionmentioning

confidence: 99%

Transcription of Genes in the Biosynthetic Pathway for Fumonisin Mycotoxins Is Epigenetically and Differentially Regulated in the Fungal Maize Pathogen Fusarium verticillioides

et al. 2012

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“…In this respect, this approach developed for eukaryotic micro-organisms has the same potential as the traditional metagenomic approach for the cloning of single genes, coding enzymes of interest, from the environment (for example, Voget et al, 2003;Yun et al, 2004). In the context of natural product discovery from the environment the metatranscriptomic approach is however limited to the independent cloning of single genes and cannot be used to recover, at once, entire biosynthetic pathways despite the fact that genes coding for the synthesis of secondary metabolites often cluster in fungal genomes (Keller and Hohn, 1997).…”

Section: Discussionmentioning

confidence: 99%

Soil eukaryotic functional diversity, a metatranscriptomic approach

et al. 2007

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To appreciate the functional diversity of communities of soil eukaryotic micro-organisms we evaluated an experimental approach based on the construction and screening of a cDNA library using polyadenylated mRNA extracted from a forest soil. Such a library contains genes that are expressed by each of the different organisms forming the community and represents its metatranscriptome. The diversity of the organisms that contributed to this library was evaluated by sequencing a portion of the 18S rDNA gene amplified from either soil DNA or reverse-transcribed RNA. More than 70% of the sequences were from fungi and unicellular eukaryotes (protists) while the other most represented group was the metazoa. Calculation of richness estimators suggested that more than 180 species could be present in the soil samples studied. Sequencing of 119 cDNA identified genes with no homologues in databases (32%) and genes coding proteins involved in different biochemical and cellular processes. Surprisingly, the taxonomic distribution of the cDNA and of the 18S rDNA genes did not coincide, with a marked under-representation of the protists among the cDNA. Specific genes from such an environmental cDNA library could be isolated by expression in a heterologous microbial host, Saccharomyces cerevisiae. This is illustrated by the functional complementation of a histidine auxotrophic yeast mutant by two cDNA originating possibly from an ascomycete and a basidiomycete fungal species. Study of the metatranscriptome has the potential to uncover adaptations of whole microbial communities to local environmental conditions. It also gives access to an abundant source of genes of biotechnological interest.

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“…Because trans-acting transcription factors, such as TOXE, TRI6, AFLR, and ORFR, should be capable of activating genes anywhere in their respective genomes, the biological rationale for the physical linkage of regulatory and regulated genes in fungal secondary metabolite gene clusters is not clear. It may be a result of their evolutionary origins and mechanisms of transmission (47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

Regulation of cyclic peptide biosynthesis in a plant pathogenic fungus by a novel transcription factor

Pedley

Walton

2001

Proc. Natl. Acad. Sci. U.S.A.

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Strains of the filamentous fungus Cochliobolus carbonum that produce the host-selective compound HC-toxin, a cyclic tetrapeptide, are highly virulent on certain genotypes of maize (Zea mays L.). Production of HC-toxin is under the control of a complex locus, TOX2, which is composed of at least seven linked and duplicated genes that are present only in toxin-producing strains of C. carbonum. One of these genes, TOXE, was earlier shown to be required for the expression of the other TOX2 genes. TOXE has four ankyrin repeats and a basic region similar to those found in basic leucine zipper (bZIP) proteins, but lacks any apparent leucine zipper. Here we show that TOXE is a DNA-binding protein that recognizes a ten-base motif (the ''tox-box'') without dyad symmetry that is present in the promoters of all of the known TOX2 genes. Both the basic region and the ankyrin repeats are involved in DNA binding. A region of TOXE that includes the first ankyrin repeat is necessary and sufficient for transcriptional activation in yeast. The data indicate that TOXE is the prototype of a new family of transcription factor, so far found only in plant-pathogenic fungi. TOXE plays a specific regulatory role in HC-toxin production and, therefore, pathogenicity by C. carbonum.

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Metabolic Pathway Gene Clusters in Filamentous Fungi

Cited by 556 publications

References 87 publications

Transcription of Genes in the Biosynthetic Pathway for Fumonisin Mycotoxins Is Epigenetically and Differentially Regulated in the Fungal Maize Pathogen Fusarium verticillioides

Transcription of Genes in the Biosynthetic Pathway for Fumonisin Mycotoxins Is Epigenetically and Differentially Regulated in the Fungal Maize Pathogen Fusarium verticillioides

Soil eukaryotic functional diversity, a metatranscriptomic approach

Regulation of cyclic peptide biosynthesis in a plant pathogenic fungus by a novel transcription factor

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