Elucidating Hydroxylation and Methylation Steps Tailoring Piericidin A1 Biosynthesis

Abstract

The piericidin A1 (<b>1</b>) gene cluster was identified from the deep-sea derived <i>Streptomyces</i> sp. SCSIO 03032. Our in vivo and in vitro experiments verified PieE as a 4′-hydroxylase and PieB2 as a 4′-<i>O</i>-methyltransferase, allowing the elucidation of the post-PKS modification steps involved in <b>1</b> biosynthesis. In addition, the shunt metabolite piericidin E1 (<b>7</b>) was identified as a novel analogue featuring a C-2/C-3 epoxy ring