title: Regulation of the biosynthesis of the macrolide antibiotic spiramycin in Streptomyces ambofaciens.
abstract: Streptomyces ambofaciens synthesizes the macrolide antibiotic spiramycin. The biosynthetic gene cluster for spiramycin has been characterized for S. ambofaciens. In addition to the regulatory gene srmR (srm22), previously identified (M. Geistlich et al., Mol. Microbiol. 6:2019-2029, 1992), three putative regulatory genes had been identified by sequence analysis. Gene expression analysis and gene inactivation experiments showed that only one of these three genes, srm40, plays a major role in the regulation of spiramycin biosynthesis. The disruption of srm22 or srm40 eliminated spiramycin production while their overexpression increased spiramycin production. Expression analysis was performed by reverse transcription-PCR (RT-PCR) for all the genes of the cluster in the wild-type strain and in the srm22 (srmR) and srm40 deletion mutants. The results from the expression analysis, together with the ones from the complementation experiments, indicated that Srm22 is required for srm40 expression, Srm40 being a pathway-specific activator that controls most, if not all, of the spiramycin biosynthetic genes.
authors.affiliation: Institut de Génétique et Microbiologie, Bâtiment 400, Université Paris-Sud, F-91405 Orsay Cedex, France.
authors.forename: Fatma
authors.initials: F
authors.lastname: Karray
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Darbon
authors.forename: Hoang Chuong
authors.initials: HC
authors.lastname: Nguyen
authors.forename: Josette
authors.initials: J
authors.lastname: Gagnat
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pernodet
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015394:Molecular Structure; D005810:Multigene Family; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015572:Spiramycin / Q000096:biosynthesis*; D013302:Streptomyces / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015572:Spiramycin
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