GntR-like SCO3932 Protein Provides a Link between Actinomycete Integrative and Conjugative Elements and Secondary Metabolism

Abstract

Streptomyces bacteria produce a plethora of secondary metabolites including the majority of medically important antibiotics. The onset of secondary metabolism is correlated with morphological differentiation and controlled by a complex regulatory network involving numerous regulatory proteins. Control over these pathways at the molecular level has a medical and industrial importance. Here we describe a GntR-like DNA binding transcription factor SCO3932, encoded within an actinomycete integrative and conjugative element, which is involved in the secondary metabolite biosynthesis regulation. Affinity chromatography, electrophoresis mobility shift assay, footprinting and chromatin immunoprecipitation experiments revealed, both in vitro and in vivo, SCO3932 binding capability to its own promoter region shared with the neighboring gene SCO3933, as well as promoters of polyketide metabolite genes, such as cpkD, a coelimycin biosynthetic gene, and actII-orf4—an activator of actinorhodin biosynthesis. Increased activity of SCO3932 target promoters, as a result of SCO3932 overproduction, indicates an activatory role of this protein in Streptomyces coelicolor A3(2) metabolite synthesis pathways.

Comparative Proteomic Analysis of Transcriptional and Regulatory Proteins Abundances in S. lividans and S. coelicolor Suggests a Link between Various Stresses and Antibiotic Production

“… The ArsR-like regulator SCO6808, which has a negative impact on antibiotic biosynthesis [ 117 ] The sensory HK CutS/SCO5863 of the TCS CutR (cluster C1)/CutS, which is thought to be involved in the regulation of copper homeostasis [ 105 ] and has a negative impact on RED and ACT biosynthesis [ 106 ]. The KorSA-like regulator SCO3932 is located upstream of a pSAM2-like ICE element and has a positive impact CPK and ACT synthesis via its direct interaction with cpkD , a coelimycin biosynthetic gene, and actII-orf4 [ 129 ]. The RR SCO5785 of the TCS SCO5784/SCO5785 has a positive impact on the production of several extracellular proteins and on antibiotics biosynthesis, and a negative one on the expression of some ribosomal genes [ 130 ].…”

“…The KorSA-like regulator SCO3932 is located upstream of a pSAM2-like ICE element and has a positive impact CPK and ACT synthesis via its direct interaction with cpkD , a coelimycin biosynthetic gene, and actII-orf4 [ 129 ].…”

Bacterial Regulatory Proteins

“…Two other papers reported research on novel regulatory proteins involved in the process of the regulation of physiological differentiation (production of bioactive secondary metabolites) in Streptomyces . Pawlik et al [ 7 ] described the role of SCO3933, a novel transcription factor belonging to the GntR family, in the regulation of antibiotic production in S. coelicolor A3(2). It specifically bound to promoters in the actinorhodin and coelimycin biosynthetic gene clusters (BGCs), and its overproduction led to increased production of both antibiotics, suggesting its positive role in the regulation of both antibiotics in S. coelicolor A3(2).…”