Identification of Early Fumonisin Biosynthetic Intermediates by Inactivation of the <i>FUM6</i> Gene in Fusarium verticillioides

Uhlig, Silvio; Busman, Mark; Shane, Deborah S.; Rønning, Helene Thorsen; Rise, Frode; Proctor, Robert H.

doi:10.1021/jf302967b

Cited by 20 publications

(18 citation statements)

References 32 publications

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“…The eight-gene deletion in fumonisin-nonproducing isolates of A. welwitschiae is consistent with the hypothesis that the absence of fum genes is the genetic basis for nonproduction in this species (Palumbo et al, 2013), because Fusarium orthologues of some of the deleted genes are required for synthesis of FB 2 (Alexander et al, 2009;Uhlig et al, 2012;Du et al, 2008). While partial deletion of the cluster would prevent fumonisin biosynthesis from occurring and provides a straightforward explanation for nonproduction in A. welwitschiae, the presence of the deletion does not rule out the possibility that the original genetic cause of nonproduction was a mutation(s) in a regulatory gene located outside the fum cluster, and that deletion of fum genes occurred after mutation of the regulatory gene.…”

Section: Maximum Likelihood Tree (Unrooted) 9 Fum Genes 6434 Characterssupporting

confidence: 83%

“…Fumonisins are a health concern because they can cause multiple diseases in experimental rodents and some livestock, and they are epidemiologically associated with several human diseases, including oesophageal cancer (Marasas et al, 2004). Fumonisins were first identified in cultures of the fungus Fusarium $25 years ago, and there is an extensive literature on production by different species as well as the genetics and biochemistry of fumonisin biosynthesis in Fusarium (Alexander et al, 2009;Rheeder et al, 1992;Uhlig et al, 2012). In contrast, fumonisin production in black aspergilli was first reported less than a decade ago (Frisvad et al, 2007), and as a result, the literature on production in Aspergillus is relatively small.…”

Section: Introductionmentioning

confidence: 99%

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Variation in the fumonisin biosynthetic gene cluster in fumonisin-producing and nonproducing black aspergilli

Susca

Proctor

Butchko

et al. 2014

Fungal Genetics and Biology

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The ability to produce fumonisin mycotoxins varies among members of the black aspergilli. Previously, analyses of selected genes in the fumonisin biosynthetic gene (fum) cluster in black aspergilli from California grapes indicated that fumonisin-nonproducing isolates of Aspergillus welwitschiae lack six fum genes, but nonproducing isolates of Aspergillus niger do not. In the current study, analyses of black aspergilli from grapes from the Mediterranean Basin indicate that the genomic context of the fum cluster is the same in isolates of A. niger and A. welwitschiae regardless of fumonisin-production ability and that full-length clusters occur in producing isolates of both species and nonproducing isolates of A. niger. In contrast, the cluster has undergone an eight-gene deletion in fumonisin-nonproducing isolates of A. welwitschiae. Phylogenetic analyses suggest each species consists of a mixed population of fumonisin-producing and nonproducing individuals, and that existence of both production phenotypes may provide a selective advantage to these species. Differences in gene content of fum cluster homologues and phylogenetic relationships of fum genes suggest that the mutation(s) responsible for the nonproduction phenotype differs, and therefore arose independently, in the two species. Partial fum cluster homologues were also identified in genome sequences of four other black Aspergillus species. Gene content of these partial clusters and phylogenetic relationships of fum sequences indicate that non-random partial deletion of the cluster has occurred multiple times among the species. This in turn suggests that an intact cluster and fumonisin production were once more widespread among black aspergilli.

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Section: Maximum Likelihood Tree (Unrooted) 9 Fum Genes 6434 Characterssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Variation in the fumonisin biosynthetic gene cluster in fumonisin-producing and nonproducing black aspergilli

Susca

Proctor

Butchko

et al. 2014

Fungal Genetics and Biology

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“…The cluster includes 17 genes, designated FUM1 through FUM3 , FUM6 through FUM8 , FUM10, FUM11 , and FUM13 through FUM21 . Of these genes, FUM1 , FUM6 , and FUM8 play key roles in fumonisin biosynthesis and mutation of these three genes resulted in little or no fumonisin biosynthesis . However, some other genes may be redundant or not required for fumonisin production.…”

Section: Discussionmentioning

confidence: 99%

Carbon Sources Influence Fumonisin Production inFusarium proliferatum

Gong

Jiang

et al. 2017

Proteomics

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Fusarium proliferatum is a worldwide fungal pathogen that produces fumonisins which are harmful to animal and human health. However, environmental factors affecting fumonisin biosynthesis in F. proliferatum are not well understood. Based on our preliminary results, in this study, we investigated the effect of sucrose or mannose as the sole carbon source on fumonisin B (FB) production by F. proliferatum and studied their underlying mechanisms via proteome and gene expression analysis. Our results showed that mannose, used as the sole carbon source, significantly blocked fumonisin B and B production by F. proliferatum as compared with the use of sucrose. Fifty-seven differentially expressed proteins were successfully identified. The downregulated proteins in the mannose-cultured strain were mainly involved in carbon metabolism, response to stress, and methionine metabolism, as compared with the sucrose-cultured strain. Moreover, quantitative real-time PCR analysis indicated that expression of several key genes involved in FB biosynthetic pathway and in transcription regulation were significantly downregulated in the mannose-cultured F. proliferatum, whereas expression of histone deacetylation-related genes were significantly upregulated. These results suggested that the blockage of FB biosynthesis by mannose was associated with the decreases in conversion of acetyl-CoA to polyketide, methionine biosynthesis, and NADPH regeneration. More importantly, milder oxidative stress, downregulated expression of genes involved in biosynthetic pathway and transcription regulation, and upregulated expression of genes with histone deacetylation possibly were responsible for the blockage of FB biosynthesis in F. proliferatum.

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“…In this case, no functionally characterized P450s from other fungi were related to these proteins, so it was not possible to suggest a potential function for this group of P450s, opening the opportunity to find new, undescribed functions for these proteins. In a sixth group, Cyp5490A1 of X. dendrorhous grouped with the proteins encoded by the fum6 and CYP505 genes of Fusarium oxysporum , which are involved in secondary metabolism reactions regarding the synthesis of the mycotoxin fumonisin and the ω-1 to ω-3 carbon hydroxylation of fatty acids, respectively [9, 55, 56]. Regarding fatty acid hydroxylation, the microbial production of hydroxyl fatty acids is of commercial interest because these compounds are widely used in the chemical, food, and cosmetic industries as starting materials for the synthesis of polymers and as additives for the manufacture of lubricants, emulsifiers, and stabilizers.…”

Section: Resultsmentioning

confidence: 99%

Characterization of the cytochrome P450 monooxygenase genes (P450ome) from the carotenogenic yeast Xanthophyllomyces dendrorhous

et al. 2017

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BackgroundThe cytochromes P450 (P450s) are a large superfamily of heme-containing monooxygenases involved in the oxidative metabolism of an enormous diversity of substrates. These enzymes require electrons for their activity, and the electrons are supplied by NAD(P)H through a P450 electron donor system, which is generally a cytochrome P450 reductase (CPR). The yeast Xanthophyllomyces dendrorhous has evolved an exclusive P450-CPR system that specializes in the synthesis of astaxanthin, a carotenoid with commercial potential. For this reason, the aim of this work was to identify and characterize other potential P450 genes in the genome of this yeast using a bioinformatic approach.ResultsThirteen potential P450-encoding genes were identified, and the analysis of their deduced proteins allowed them to be classified in ten different families: CYP51, CYP61, CYP5139 (with three members), CYP549A, CYP5491, CYP5492 (with two members), CYP5493, CYP53, CYP5494 and CYP5495. Structural analyses of the X. dendrorhous P450 proteins showed that all of them have a predicted transmembrane region at their N-terminus and have the conserved domains characteristic of the P450s, including the heme-binding region (FxxGxRxCxG); the PER domain, with the characteristic signature for fungi (PxRW); the ExxR motif in the K-helix region and the oxygen-binding domain (OBD) (AGxDTT); also, the characteristic secondary structure elements of all the P450 proteins were identified. The possible functions of these P450s include primary, secondary and xenobiotic metabolism reactions such as sterol biosynthesis, carotenoid synthesis and aromatic compound degradation.ConclusionsThe carotenogenic yeast X. dendrorhous has thirteen P450-encoding genes having potential functions in primary, secondary and xenobiotic metabolism reactions, including some genes of great interest for fatty acid hydroxylation and aromatic compound degradation. These findings established a basis for future studies about the role of P450s in the carotenogenic yeast X. dendrorhous and their potential biotechnological applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3942-9) contains supplementary material, which is available to authorized users.

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Identification of Early Fumonisin Biosynthetic Intermediates by Inactivation of the FUM6 Gene in Fusarium verticillioides

Cited by 20 publications

References 32 publications

Variation in the fumonisin biosynthetic gene cluster in fumonisin-producing and nonproducing black aspergilli

Variation in the fumonisin biosynthetic gene cluster in fumonisin-producing and nonproducing black aspergilli

Carbon Sources Influence Fumonisin Production inFusarium proliferatum

Characterization of the cytochrome P450 monooxygenase genes (P450ome) from the carotenogenic yeast Xanthophyllomyces dendrorhous

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