Small NRPS-like enzymes in Aspergillus sections Flavi and Circumdati selectively form substituted pyrazinone metabolites

Aspergillus fungi produce mycotoxins that are detrimental to human and animal health. Two sections of aspergilli particular importance cereal food crops such as corn barley. section Flavi species like A. flavus parasiticus aflatoxins, while Circumdati ochraceus sclerotiorum ochratoxin Mitigating these toxins in feed is a critical ongoing worldwide effort. We have previously investigated biosynthetic gene clusters linked fungal virulence corn. found one cluster, asa , responsible for the production aspergillic acid, an iron-binding, hydroxamic acid-containing pyrazinone metabolite. Furthermore, we cluster present many other aflatoxin- ochratoxin-producing aspergilli. The core encodes small nonribosomal peptide synthetase-like (NRPS-like) protein AsaC. swapped asaC ortholog from into replacing its native copy, also cloned both orthologs Saccharomyces cerevisiae . show AsaC only containing adenylation-thiolation-reductase (ATR) domains, can selectively biosynthesize distinct natural products: deoxyaspergillic acid flavacol, respectively. Because products their implicated variety important microbe-host interactions, uncovering function selectivity enzymes involved could lead strategies ultimately benefit