title: 5S clavam biosynthetic genes are located in both the clavam and paralog gene clusters in Streptomyces clavuligerus.
abstract: The Streptomyces clavuligerus clavam gene cluster was examined to identify genes specifically involved in 5S clavam biosynthesis. A reduction/loss of 5S clavam production was seen in cvm2 and cvm5 gene mutants, and a clavam metabolite not previously observed, 2-carboxymethylideneclavam, accumulated in the cvm5 mutant. Disruption of additional genes from the region of the clavam cluster did not have any effect on 5S clavam production. Examination of the paralog gene cluster region for 5S clavam biosynthetic genes led to the identification of cvm6P and cvm7P, which encode a putative aminotransferase and a transcriptional regulator, respectively. Mutants defective in cvm6P and cvm7P were completely blocked in 5S clavam but not clavulanic acid production. The loss of 5S clavam production in cvm7P mutants suggests that this gene encodes a transcriptional regulator specific for 5S clavam metabolite biosynthesis.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Kapil
authors.initials: K
authors.lastname: Tahlan
authors.forename: Cecilia
authors.initials: C
authors.lastname: Anders
authors.forename: Annie
authors.initials: A
authors.lastname: Wong
authors.forename: Roy H
authors.initials: RH
authors.lastname: Mosher
authors.forename: Perrin H
authors.initials: PH
authors.lastname: Beatty
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brumlik
authors.forename: Allison
authors.initials: A
authors.lastname: Griffin
authors.forename: Claire
authors.initials: C
authors.lastname: Hughes
authors.forename: John
authors.initials: J
authors.lastname: Griffin
authors.forename: Barry
authors.initials: B
authors.lastname: Barton
authors.forename: Susan E
authors.initials: SE
authors.lastname: Jensen
mesh_terms: D015139:Blotting, Southern; D002853:Chromatography, Liquid; D019818:Clavulanic Acid / Q000096:biosynthesis; D002969:Clavulanic Acids / Q000096:biosynthesis*; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D013058:Mass Spectrometry; D005810:Multigene Family; D016254:Mutagenesis, Insertional; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002969:Clavulanic Acids; D004269:DNA, Bacterial; C483963:clavam; D019818:Clavulanic Acid