AA contributed to design, laboratory experiments, analysed data, and the writing of manuscript. SFN contributed to laboratory experiments, data analysis and writing of manuscript. IO, GH and BD contributed to conception and design, data analysis and the writing of manuscript. All authors have read and approved the final manuscript.”
“Background Streptomyces are Gram-positive eubacteria that are the major natural source of antibiotics, producing about half of all known microbial antibiotics [1]. This genus also
has a complex life cycle, in which spores germinate to form a substrate mycelium of branching hyphae on solid medium, from which branches grow into the air, such multi-nucleoid aerial hyphae ultimately becoming septated to form chains of unigenomic AZD1208 spores [2, 3]. Streptomyces coelicolor is the most studied Streptomyces species and an excellent model for studying antibiotic production and differentiation [4]. It produces several chemically different antibiotics, including HM781-36B concentration the blue-pigmented actinorhodin (Act), red-pigmented undecylprodigiosin (Red), calcium-dependent
antibiotic (CDA) and plasmid SCP1-encoded methylenomycin (Mmy). Pathway-specific regulatory genes, e.g. actII-orf4, redD, cdaR and mmyB, are required for initiating transcription of the corresponding antibiotics biosynthetic gene clusters; while pleiotropic regulators, e.g. AfsR, often affect multiple secondary metabolism [5, 6]. By using S. coelicolor as a model system, two dozen genes (bld and whi),
most of them encoding regulatory proteins, important for initiation of aerial mycelium formation and sporulation have been identified [7]. More than 20 other genes from primary metabolism (e.g. citA encoding citrate synthase; [8]) and stress-response (rsrA for oxidation-sensing anti-sigma protein; [9]) etc also affect Streptomyces differentiation, indicating that the regulatory signaling cascades for aerial growth and sporulation extensively interact with metabolic, Loperamide morphological, homeostatic and stress-related checkpoints [10]. Recently, several key genes affecting apical growth, chromosome segregation and cell division (e.g. divIVA, sffA, ftsZ, ftsQ, ftsK and parA/B; [11–17]) have been identified. Here we describe identification of a cluster of six co-transcribed genes cmdABCDEF (encoding five membrane proteins and one membrane-located ATP/GTP-binding protein) in S. coelicolor that affect sporulation and antibiotic production. Results Co-transcription of six genes SCO4126-4131 of S. coelicolor Earlier work indicated that the six co-transcribed genes (SLP2.19-23 or pQC542.1c-6c) of Streptomyces linear plasmid SLP2 are required for plasmid conjugal transfer [18, 19]. Interestingly, three genes SLP2.21-23 resembled SCO4127-4129 of S. coelicolor chromosome (identities were 33% [133/393], 29% [56/193] and 22% [97/435] respectively), which were also located in a cluster of six genes SCO4126-4131 (Figure 1A). The transcription directions of SCO4126-4131 were same.