ANDRIMID AND MOIRAMIDES A-C, METABOLITES PRODUCED IN CULTURE BY A MARINE ISOLATE OF THE BACTERIUM PSEUDOMONAS-FLUORESCENS - STRUCTURE ELUCIDATION AND BIOSYNTHESIS

Andrimid (1) and moiramides A-C (2-4) have been isolated from solid agar cultures of a marine isolate of the bacterium Pseudomonas fluorescens. The chemical structures of moiramides A-C (2-4) have been elucidated by analysis of spectroscopic data. Andrimid (1) and moiramide B (3) were found to exhibit potent in vitro inhibition of methicillin resistant Staphylococcus aureus. Stable isotope incorporation experiments have been used to elucidate the biogenesis of the acylsuccinimide fragment of andrimid (1) that is essential for antimicrobial activity. These experiments demonstrated that the acylsuccinimide fragment is derived from a combination of acetate and amino acid building blocks. It has been proposed that the biosynthesis proceeds through a dipeptide-like intermediate formed from gamma-amino-beta-keto acids that are in turn formed from valine and glycine homologated with acetate, presumably via malonyl-CoA.