Microbisporicin gene cluster reveals unusual features of lantibiotic biosynthesis in actinomycetes.
Lantibiotics are ribosomally synthesized, posttranslationally modified peptide antibiotics. The biosynthetic gene cluster for microbisporicin, a potent lantibiotic produced by the actinomycete Microbispora corallina containing chlorinated tryptophan and dihydroxyproline residues, was identified by genome scanning and isolated from an M. corallina cosmid library. Heterologous expression in Nonomuraea sp. ATCC 39727 confirmed that all of the genes required for microbisporicin biosynthesis were present in the cluster. Deletion, in M. corallina, of the gene (mibA) predicted to encode the prepropeptide abolished microbisporicin production. Further deletion analysis revealed insights into the biosynthesis of this unusual and potentially clinically useful lantibiotic, shedding light on mechanisms of regulation and self-resistance. In particular, we report an example of the involvement of a tryptophan halogenase in the modification of a ribosomally synthesized peptide and the pathway-specific regulation of an antibiotic biosynthetic gene cluster by an extracytoplasmic function sigma factor-anti-sigma factor complex.
Foulston
Lucy C
LC
John Innes Centre, Norwich NR4 7UH, United Kingdom.
Bibb
Mervyn J
MJ
D039903:Actinobacteria / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001430:Bacteriocins / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D023061:Gene Order; D005818:Genetic Engineering; D015698:Genomic Library; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001430:Bacteriocins; D010455:Peptides; D011498:Protein Precursors; C528150:microbisporicin