Regulation of secondary metabolism in fungi

Secondary metabolites (idiolites) are structurally diverse and unusual, generally are produced in mixtures with other members of the same chemical family, and usually are formed at low specific growth rates. In batch cultures, processes leading to the production of idiolites are often sequential; the cultures exhibit a distinct growth phase (trophophase) followed by a production phase (idiophase). However, trophophase and idiophase may overlap. Timing depends on the nutritional environment presented to the culture. Specific mechanisms regulating the onset of idiolite synthesis include repression by sources of carbon, nitrogen and phosphate and enzyme induction. Cessation of idiolite biosynthesis occurs via decay of idiolite synthetases as well as feedback inhibition and repression of these enzymes. With regard to control of mycotoxin biosynthesis, most studies have been done on ergot alkaloid, aflatoxin and patulin formation. Ergot alkaloid formation is mainly controlled by carbon source regulation (glucose), phosphate repression, induction (tryptophan), growth rate and feedback inhibition (agroclavine and elymoclavine). Aflatoxin biosynthesis is controlled by nitrogen source repression (nitrate) and induction (glucose); zinc stimulates production in an unknown manner. Patulin production is regulated by nitrogen source repression, induction (6—methylsalicylic acid), growth rate and synthetase decay.