Isolation and structure revision of the actin-binding macrolide rhizopodin from Myxococcus stipitatus (Myxobacteria)

Abstract

Rhizopodin was isolated as cytostatic and weakly antifungal macrolide ( 1) and later characterized as potent actin-depolymerizing agent. It is produced by the myxobacterium Myxococcus stipitatus, which enables a fermentative supply of the drug for biological studies. We here report a revised structure that characterizes rhizopodin ( 2) as the first known dimeric bis-lactone exhibiting side chains that terminate in N-methyl-vinylformamide groups, which are otherwise found in smaller marine toxins also targeting the actin cytoskeleton. Compound 2 might function as bivalent inhibitor forming ternary complexes with actin which would explain its high efficacy.