New insights into the disulfide bond formation enzymes in epidithiodiketopiperazine alkaloids.

ABSTRACT: Epidithiodiketopiperazines (ETPs) are a group of bioactive fungal natural products and structurally feature unique transannular disulfide bridges between α, α or α, β carbons. However, no enzyme has yet been demonstrated to catalyse α, β-disulfide bond formation in these molecules. Through genome mining and gene deletion approaches in Trichoderma hypoxylon, we identified a putative biosynthetic gene cluster of pretrichodermamide A (1), which requires a FAD-dependent oxidoreductase, TdaR, for the irregular α, β-disulfide formation in 1 biosynthesis. In vitro assays of TdaR, together with AclT involved in aspirochlorine and GliT involved in gliotoxin biosynthesis, proved that all three enzymes catalyse not only the conversion of red-pretrichodermamide A (4)

SUBMITTER: Liu H 

PROVIDER: S-EPMC8179532 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature