Microbisporicin gene cluster reveals unusual features of lantibiotic biosynthesis in actinomycetes.

Abstract:

: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.

authors

Foulston LC,Bibb MJ

doi

10.1073/pnas.1008285107

subject

Has Abstract

pub_date

2010-07-27 00:00:00

pages

13461-6

issue

30

eissn

0027-8424

issn

1091-6490

pii

1008285107

journal_volume

107

pub_type

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