Nonribosomal biosynthesis of fusaricidins by Paenibacillus polymyxa PKB1 involves direct activation of a D-amino acid.
Paenibacillus polymyxa PKB1 produces fusaricidins, a family of lipopeptide antibiotics that strongly inhibits the growth of many plant pathogenic fungi. The fusaricidin biosynthetic gene cluster was cloned and sequenced, and it spans 32.4 kb, including an open reading frame (fusA) encoding a six-module nonribosomal peptide synthetase. The second, fourth, and fifth modules of fusaricidin synthetase each contain an epimerization domain, consistent with the structure of fusaricidins. However, no epimerization domain is found in the sixth module, corresponding to D-Ala. This sixth adenylation domain was produced at a high level in Escherichia coli and is shown to activate D-Ala specifically, providing evidence for direct activation of a D-amino acid by a prokaryotic peptide synthetase. The fusaricidin gene cluster also includes genes involved in the biosynthesis of the lipid moiety, but no genes for resistance, regulation, or transport functions were encountered.
Li
Jingru
J
Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
Jensen
Susan E
SE
D000249:Adenosine Monophosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D047630:Depsipeptides / Q000096:biosynthesis* / Q000737:chemistry; D038101:Insulator Elements / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D046908:Peptide Biosynthesis, Nucleic Acid-Independent / Q000235:genetics*; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013379:Substrate Specificity
D000596:Amino Acids; D047630:Depsipeptides; D000249:Adenosine Monophosphate; D010453:Peptide Synthases