The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides

The potent antibacterial lanthipeptide microvionin, isolated from a culture of Microbacterium arborescens , exhibits a new triamino-dicarboxylic acid moiety, termed avionin, and an unprecedented N-terminal guanidino fatty acid. We identified the corresponding biosynthetic gene cluster and reconstituted central steps of avionin biosynthesis in vitro. Genome mining and isolation of nocavionin from Nocardia terpenica revealed a widespread distribution of this lanthipeptide class, termed lipolanthines, which may be useful as future antimicrobial drugs. The antibacterial microvionin contains two new lanthipeptide modifications, a triamino-dicarboxylic acid (avionin) and an N-terminal guanidino fatty acid, that lead to the establishment of the lipolanthine natural product class.