Elucidating Hydroxylation and Methylation Steps Tailoring Piericidin A1 Biosynthesis

The piericidin A1 (1) gene cluster was identified from the deep-sea derived Streptomyces sp. SCSIO 03032. Our in vivo and in vitro experiments verified PieE as a 4'-hydroxylase and PieB2 as a 4'-O-methyltransferase, allowing the elucidation of the post-PKS modification steps involved in 1 biosynthesis. In addition, the shunt metabolite piericidin El (7) was identified as a novel analogue featuring a C-2/C-3 epoxy ring.