Regulation of Aspergillus flavus aflatoxin biosynthesis and development

The filamentous fungus Aspergillus flavus produces a family of potent mutagenic and carcinogenic polyketide-derived compounds collectively known as aflatoxins. These secondary metabolites contaminate a number of oilseed crops during growth of the fungus and this can result in severe negative economic and health impacts. The biosynthesis and regulation of these toxins represent one of most studied areas of all the fungal secondary metabolites. Much of the information obtained on the AF biosynthetic genes and regulation of AF biosynthesis was obtained through studies using A. flavus and A. parasiticus and also the model fungus Aspergillus nidulans that produces sterigmatocystin (ST), the penultimate precursor to AF. There has long been anecdotal evidence of a genetic linkage between production of secondary metabolites and fungal morphogenesis however the exact mechanism of this relationship was not clear. A breakthrough in the genetic mechanisms governing AF production and A. flavus development was made upon the discovery in A. nidulans of a G-protein-mediated signaling pathway that regulated both ST biosynthesis and asexual conidiation. Further studies in A. nidulans and A. flavus and also of the fungus-host plant interaction have identified a number of genetic factors that link secondary metabolism and morphological differentiation processes in A. flavus as well as filamentous fungi in general. The focus of this review is to provide an overview of research that characterized the genes involved in the biosynthesis and regulation of AF in A. flavus, how environmental and nutritional factors control expression of these genes, and the role of global regulators in AF production, fungal development and virulence. The impact of fungal whole genome sequence and microarray technology in the identification of novel genes involved in the regulation of AF production and development as well as virulence are also discussed.