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PMID: 8439156 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Biosynthesis of the lantibiotic subtilin is regulated by a histidine kinase/response regulator system.

Applied and environmental microbiology ·Vol. 59 ·No. 1 ·1993-01-00 ·Pages 296-303

Klein C, Kaletta C, Entian KD

Abstract

Subtilin is a lanthionine-containing peptide antibiotic (lantibiotic) which is produced by Bacillus subtilis ATCC 6633. Upstream from the structural gene of subtilin, spaS, three genes (spaB, spaT, and spaC) which are involved in the biosynthesis of subtilin have been identified (C. Klein, C. Kaletta, N. Schnell, and K.-D. Entian, Appl. Environ. Microbiol. 58:132-142, 1992). By using a hybridization probe specific for these genes, the DNA region downstream from spaS was isolated. Further subcloning revealed a 5.2-kb KpnI-HindIII fragment on which two open reading frames, spaR and spaK, were identified approximately 3 kb downstream from spaS. The spaR gene encodes an open reading frame of 220 amino acids with a predicted molecular mass of 25.6 kDa. SpaR shows 35% similarity to positive regulatory factors OmpR and PhoB. The spaK gene encodes an open reading frame of 387 amino acids with a predicted molecular mass of 44.6 kDa and was highly similar to histidine kinases previously described (PhoM, PhoR, and NtrB). Hydrophobicity blots suggested two membrane-spanning regions. Thus, spaR and spaK belong to a recently identified family of environmentally responsive regulators. These results indicated a regulatory function of spaR and spaK in subtilin biosynthesis. Indeed, batch culture experiments confirmed the regulation of subtilin biosynthesis starting in the mid-logarithmic growth phase and reaching its maximum in the early stationary growth phase. Gene deletions within spaR and spaK yielded subtilin-negative mutants, which confirms that subtilin biosynthesis is under the control of a two-component regulatory system.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms
Amino Acid Sequence Anti-Bacterial Agents/biosynthesis Bacillus subtilis/genetics,metabolism Bacterial Proteins Bacteriocins Base Sequence Gene Deletion Gene Expression Regulation, Bacterial/drug effects Genes, Bacterial Histidine Kinase Molecular Sequence Data Mutation Peptides Peptides, Cyclic/biosynthesis,genetics,isolation & purification Phenotype Protein Kinases/genetics,physiology Sequence Homology, Amino Acid Signal Transduction
Chemicals
Anti-Bacterial Agents Bacterial Proteins Bacteriocins Peptides Peptides, Cyclic Protein Kinases Histidine Kinase subtilin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Klein C
Institute for Microbiology, Johann Wolfgang Goeth-Universität, Frankfurt, Germany.
Kaletta C
Entian K D
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39 references, click to expand
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Article Info
Journal
Applied and environmental microbiology
Abbr.
Appl Environ Microbiol
ISSN
0099-2240
DOI
10.1128/aem.59.1.296-303.1993
Published
1993-01-00
Pages
296-303
Language
English
Region
United States
NLM ID
7605801
PMCID
PMC202094
Subset
IM
Databases
GENBANK
L07785, X62978, X62979, X62980, X62981, X62986, X62987, X62988, X62989, X62990
External Links
PubMed source DOI: 10.1128/aem.59.1.296-303.1993 PMC Full Text View journal details
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