Biosynthesis of helvolic acid and identification of an unusual C-4-demethylation process distinct from sterol biosynthesis.

ABSTRACT: Fusidane-type antibiotics represented by helvolic acid, fusidic acid and cephalosporin P₁ are a class of bacteriostatic agents, which have drawn renewed attention because they have no cross-resistance to commonly used antibiotics. However, their biosynthesis is poorly understood. Here, we perform a stepwise introduction of the nine genes from the proposed gene cluster for helvolic acid into Aspergillus oryzae NSAR1, which enables us to isolate helvolic acid (~20 mg L^-1) and its 21 derivatives. Anti-Staphylococcus aureus assay reveals that the antibacterial activity of three intermediates is even stronger than that of helvolic acid. Notably, we observe an unusual C-4 demethylation process mediated by a promiscuous short-chain dehydrogenase/reductase (HelC) and a cytoch

SUBMITTER: Lv JM 

PROVIDER: S-EPMC5696383 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature