Biosynthetic mechanism and regulation of zearalenone in Fusarium graminearum

Abstract

Zearalenone (ZEA) is an estrogenic polyketide-derived mycotoxin that is produced by several Fusarium spp. This mycotoxin is often found in F. graminearum-infected cereals and causes a number of illnesses in animals, including humans. The genetic information of the ZEA biosynthetic pathway has been characterized in F. graminearum using forward and reverse genetic approaches. Four genes responsible for ZEA biosynthesis, including two polyketide synthase (PKS) genes, are located in the ZEA biosynthetic gene cluster. In addition to two PKSs, ZEB1 and ZEB2 encode an isoamyl alcohol oxidase and a transcription activator carrying a basic leucine zipper (bZIP) DNA-binding domain, respectively. ZEB2 produces two isoforms (ZEB2L and ZEB2S) via an alternative promoter. ZEB2L and ZEB2S interact with each other and participate in the autoregulation of ZEB2 expression as an activator and an inhibitor, respectively, during ZEA biosynthesis. The catalytic and regulatory subunits of the cyclic AMP (cAMP)-dependent protein kinase A (PKA) pathway in F. graminearum, CPK1 and PKR, negatively regulate ZEA biosynthesis. In particular, it was found that the PKA pathway regulates ZEB2L transcriptionally and post-transcriptionally during ZEA production. These results increase our understanding of regulatory mechanisms underlying ZEA biosynthesis in F. graminearum.