RESUMO
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.
Assuntos
Antibacterianos/farmacologia , Lipopeptídeos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Ribossomos/química , Antibacterianos/biossíntese , Antibacterianos/química , Lipopeptídeos/biossíntese , Lipopeptídeos/química , Testes de Sensibilidade Microbiana , Ribossomos/metabolismoRESUMO
Anti-Bredt bridged bicyclo[3.2.1] gamma-lactams were designed as inhibitors of penicillin binding proteins (PBPs). The compounds were prepared by a carbenoid insertion into a lactam N-H bond. Their weak antibacterial activity could either be explained by a poor chemical stability or by unfavorable steric interactions of the methylene bridge of the gamma-lactam with the targeted enzymes.