Biosynthesis of 9‑Methylstreptimidone Involves a New Decarboxylative Step for Polyketide Terminal Diene Formation

Abstract

9-Methylstreptimidone is a glutarimide antibiotic showing antiviral, antifungal, and antitumor activities. Genome scanning, bioinformatics analysis, and gene inactivation experiments reveal a gene cluster responsible for the biosynthesis of 9-methylstreptimidone in <i>Streptomyces himastatinicus</i>. The unveiled machinery features both acyltransferase- and thioesterase-less iterative use of module 5 as well as a branching module for glutarimide generation. Impressively, inactivation of <i>smdK</i> leads to a new carboxylate analogue unveiling a new mechanism for polyketide terminal diene formation