Two separate key enzymes and two pathway‐specific transcription factors are involved in fusaric acid biosynthesis in F usarium fujikuroi

Abstract

Summary Fusaric acid ( FSA ) is a mycotoxin produced by several fusaria, including the rice pathogen F usarium fujikuroi . Genes involved in FSA biosynthesis were previously identified as a cluster containing a polyketide synthase ( PKS )‐encoding ( FUB1 ) and four additional genes ( FUB2 ‐ FUB5 ). However, the biosynthetic steps leading to FSA as well as the origin of the nitrogen atom, which is incorporated into the polyketide backbone, remained unknown. In this study, seven additional cluster genes ( FUB6 ‐ FUB12 ) were identified via manipulation of the global regulator FfSge1 . The extended FUB gene cluster encodes two Zn(II) 2 Cys 6 transcription factors: F ub10 positively regulates expression of all FUB genes, whereas F ub12 is involved in the formation of the two FSA derivatives, i.e. dehydrofusaric acid and fusarinolic acid, serving as a detoxification mechanism. The major facilitator superfamily transporter F ub11 functions in the export of FSA out of the cell and is essential when FSA levels become critical. Next to F ub1, a second key enzyme was identified, the non‐canonical non‐ribosomal peptide synthetase F ub8. Chemical analyses of generated mutant strains allowed for the identification of a triketide as PKS product and the proposition of an FSA biosynthetic pathway, thereby unravelling the unique formation of a hybrid metabolite consisting of this triketide and an amino acid moiety.

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