A Single Cluster of Coregulated Genes Encodes the Biosynthesis of the Mycotoxins Roquefortine C and Meleagrin in Penicillium chrysogenum

SummaryA single gene cluster of Penicillium chrysogenum contains genes involved in the biosynthesis and secretion of the mycotoxins roquefortine C and meleagrin. Five of these genes have been silenced by RNAi. Pc21g15480 (rds) encodes a nonribosomal cyclodipeptide synthetase for the biosynthesis of both roquefortine C and meleagrin. Pc21g15430 (rpt) encodes a prenyltransferase also required for the biosynthesis of both mycotoxins. Silencing of Pc21g15460 or Pc21g15470 led to a decrease in roquefortine C and meleagrin, whereas silencing of the methyltransferase gene (Pc21g15440; gmt) resulted in accumulation of glandicolin B, indicating that this enzyme catalyzes the conversion of glandicolin B to meleagrin. All these genes are transcriptionally coregulated. Our results prove that roquefortine C and meleagrin derive from a single pathway.

► A single gene cluster encodes the biosynthesis of two different mycotoxins ► Roquefortine and meleagrin are formed by a nonribosomal cyclodipeptide synthetase ► The His-Trp cyclodipeptide is prenylated by a reverse prenyltransferase ► The mutant silenced in the methyltransferase (gmt) accumulates glandicolin B