An Aspergillus flavus secondary metabolic gene cluster containing a hybrid PKS–NRPS is necessary for synthesis of the 2-pyridones, leporins

Cary, Jeffrey W.; Uka, Valdet; Han, Zheng; Buyst, Dieter; Harris-Coward, Pamela Y.; Ehrlich, Kenneth C.; Wei, Qijian; Bhatnagar, Deepak; Dowd, Patrick F.; Martens, Stacey L.; Calvo, Ana M.; Martins, José; Vanhaecke, Lynn; Coenye, Tom; Saeger, Sarah De; Mavungu, José Diana Di

doi:10.1016/j.fgb.2015.05.010

Cited by 65 publications

(86 citation statements)

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“…The authors identified eight clusters demonstrating high expression levels under their conditions and eleven clusters correlating with sclerotial development. In addition to asparasone and aflavarin mentioned previously, the cluster for leporin production was also among those predicted 15) . doi: 10.14252/foodsafetyfscj.2017024 To date there has not been numerous use of RNA-seq combined with gene knockout technology in A. flavus, however RNA-seq was conducted on the small sclerotia producing A. flavus strain AF70 to examine the effects of knocking out the zinc-finger transcription factor nsdC.…”

Section: -2 Rna Sequencingsupporting

confidence: 70%

“…Inactivation of the A. flavus leporin cluster (see section 5-2) Zn(2)-Cys(6) transcription factor gene, lepE, resulted in significant down-regulation of all the cluster genes 15) . Over-expression of lepE produced orange-red pigmented hyphae due to the synthesis of the 2-pyridone, leporin B.…”

Section: -2 Cluster-specific Regulationmentioning

confidence: 99%

“…One of these clusters was shown to be responsible for the production of the indole tetramic acid, cyclopiazonic acid 140) while the second cluster produced a family of 2-pyridones known as leporins 15) . TePaske et al 141) reported on the production of the antiinsectan compound, leporin A, in the fungus Aspergillus leporis, however there had been no previous reports of leporin production in A. flavus.…”

Section: -2 Leporin Clustermentioning

confidence: 99%

“…TePaske et al 141) reported on the production of the antiinsectan compound, leporin A, in the fungus Aspergillus leporis, however there had been no previous reports of leporin production in A. flavus. In addition to the PKS-NRPS (AFLA_066840, lepA), the leporin cluster was predicted to encode an additional 14 genes that could be involved in metabolite production 15) . An A. flavus ∆lepA mutant showed no significant differences in metabolite production compared to that of an isogenic control strain, indicating that the genes responsible for leporin biosynthesis were not being expressed or expressed at extremely low levels.…”

Section: -2 Leporin Clustermentioning

confidence: 99%

“…3). Liquid chromatography and high resolution mass spectrometry (LC-HRMS) analysis of the OE::lepE extracts revealed a metabolite of m/z (M+H)=352.1902 that represented a demethylated leporin A precursor designated leporin B 15) . Additionally, a metabolite of m/z (M+H)=336.1959 was also produced that represented the N-demethoxy derivative of leporin A, designated leporin C. While leporin B had been previously reported to be produced by an unidentified fungus 142) , this was the first report of production of leporin C. Interestingly, metabolites were identified in the OE::lepE strain that were consistent with homodimers of both leporin B and C.…”

Section: -2 Leporin Clustermentioning

confidence: 99%

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<i>Aspergillus flavus</i> Secondary Metabolites: More than Just Aflatoxins

et al. 2018

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Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of these secondary metabolites have been identified from A. flavus cultures, analysis of the genome has predicted the existence of at least 56 secondary metabolite gene clusters. Many of these gene clusters are not expressed during growth of the fungus on standard laboratory media. This presents researchers with a major challenge of devising novel strategies to manipulate the fungus and its genome so as to activate secondary metabolite gene expression and allow identification of associated cluster metabolites. In this review, we discuss the genetic, biochemical and bioinformatic methods that are being used to identify previously uncharacterized secondary metabolite gene clusters and their associated metabolites. It is important to identify as many of these compounds as possible to determine their bioactivity with respect to fungal development, survival, virulence and especially with respect to any potential synergistic toxic effects with aflatoxin.

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Section: -2 Rna Sequencingsupporting

confidence: 70%

Section: -2 Cluster-specific Regulationmentioning

confidence: 99%