Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in J1074.

Heterologous expression has emerged as an effective strategy in activating cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster derived from marine sp. HDN155000 in the chassis host J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z () contains a rare thiomethyl group, angumycinone T () has a novel oxo-bridge formed between C12a and C4, and angumycinone X () showed cytotoxicity toward K562 and NCI-H446/EP cell lines.