Biosynthesis of paenibacillin, a lantibiotic with N-terminal acetylation, by Paenibacillus polymyxa

Paenibacillin, a recently-discovered lantibiotic from Paenibacillus polymyxa OSY-DF, showed potency against Listeria monocytogenes, methicillin-resistant Staphylococcus aureus and other Gram-positive bacteria. The chemical structure of paenibacillin has been determined previously. This study was initiated to investigate the biosynthesis of paenibacillin, and to reveal unique features in its biosynthetic pathway. Paenibacillin structural gene (paeA) was identified by polymerase chain reaction (PCR) analysis. The complete biosynthetic gene cluster was revealed by whole genome sequencing of the producer strain. The paenibacillin gene cluster (11.7 kb) comprises 11 open reading frames (ORFs) encoding proteins for production, modification, regulation, immunity and transportation of the lantibiotic. Disruption of the gene encoding lantibiotic dehydratase (PaeB) completely eliminated the production of paenibacillin. The cluster includes a gene encoding a putative acetylase (PaeN), which may catalyze the N-terminal acetylation of paenibacillin during its biosynthesis. This finding supports the results of a previous chemical analysis, reporting an acetyl moiety uniquely located at paenibacillin N-terminus. Results of this study may expedite efforts to design effective lantibiotic drugs and facilitate attempts to increase the productivity of the lantibiotic-producing strain.