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.Streptomyces species are Gram-positive, soil-inhabiting, filamentous bacteria that undergo a complex process of morphological differentiation and produce a great variety of secondary metabolites, including antibiotics with important applications in human medicine and in agriculture. These secondary metabolites are synthesized by complex pathways that utilize primary metabolites as building blocks. The genes required for

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

“…TylR, a homologue of CSRs for carbomycin and spiramycin biosynthesis (205), is the direct activator of the tylosin biosynthetic genes. The expression of tylR requires the combined action of two SARPs, TylS and TylU (which is described as a "SARP helper").…”

Post-PKS Tailoring Steps of the Spiramycin Macrolactone Ring in Streptomyces ambofaciens

“…S3 in the supplemental material), indicating that srm42 and srm43 are not involved in the reduction of the platenolide I C-9 keto group or in spiramycin biosynthesis. Thus, the srm gene cluster, previously delimited at srm43 (26), most likely ends with srm41.…”

— Cadmium Bioremediation by a Resistant Streptomyces Strain

“…Some of the strains can be associated with contaminated soils, e.g., Lentzea with heavy-metal contaminated soils (Haferburg 2007). Others were reported for specifi c abilities to degrade some compounds, such as S. iakyrus and parathion (De Pasquale et al 2008) and S. albogriseolus and latex (Gallert 2000), to produce antibiotics such as S. achromogenes and streptozotocin, rubradirin (Maharjan et al 2003) and tomaymycin (Li et al 2009), S. ambofaciens and spiramycin (Karray et al 2010), S. lincolnensis and lyncomicine (Koběrská et al 2008) and to produce enzymes, such as S. fradie with keratolytic activity (Noval and Nickerson 1958). However to the best of our knowledge there are no reports in the literature about Streptomyces or Lentzea capacity to grow in soils or media with high concentrations of boron compounds.…”