CmdABCDEF, a cluster of genes encoding membrane proteins for differentiation and antibiotic production in Streptomyces coelicolorA3(2)

Pengfei Xie,Zhongjun Qin,Ana Zeng

doi:10.1186/1471-2180-9-157

Pengfei Xie, Zhongjun Qin + Show 1 more

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https://doi.org/10.1186/1471-2180-9-157

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Abstract

BackgroundStreptomyces coelicolor is the most studied Streptomyces species and an excellent model for studying differentiation and antibiotic production. To date, many genes have been identified to be required for its differentiation (e.g. bld genes for aerial growth and whi genes for sporulation) and antibiotics production (including actII-orf4, redD, cdaR as pathway-specific regulatory genes and afsR, absA1/A2 as pleiotropic regulatory genes).ResultsA gene cluster containing six genes (SCO4126-4131) was proved to be co-transcribed in S. coelicolor. Deletions of cmdABCDEF (SCO4126-4131) displayed defective sporulation including formation of aberrant branches, and abnormalities in chromosome segregation and spore septation. Disruption mutants of apparently orthologous genes of S. lividans and S. avermitilis also showed defective sporulation, implying that the role of these genes is similar among Streptomyces. Transcription of cmdB, and therefore presumably of the whole operon, was regulated developmentally. Five of the encoded proteins (CmdA, C, D, E, F) were predicted membrane proteins. The other, CmdB, a predicted ATP/GTP-binding protein with an ABC-transporter-ATPase domain shown here to be essential for its function, was also located on the cell membrane. These results indicate that CmdABCDEF proteins mainly affect Streptomyces differentiation at an early stage of aerial hyphae formation, and suggest that these proteins may form a complex on cell membrane for proper segregation of chromosomes. In addition, deletions of cmdABCDEF also revealed over-production of blue-pigmented actinorhodin (Act) via activation of transcription of the pathway-specific regulatory gene actII-orf4 of actinorhodin biosynthesis.ConclusionIn this study, six co-transcribed genes cmdABCDEF were identified by their effects on differentiation and antibiotic production in Streptomyces coelicolor A3(2). These six membrane-located proteins are possibly assembled into a complex to function.

Highlights

Streptomyces coelicolor is the most studied Streptomyces species and an excellent model for studying differentiation and antibiotic production
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]
Three genes SLP2.21-23 resembled SCO4127-4129 of S. coelicolor chromosome, which were located in a cluster of six genes SCO4126-4131 (Figure 1A)

Summary

Introduction

Streptomyces coelicolor is the most studied Streptomyces species and an excellent model for studying differentiation and antibiotic production. Many genes have been identified to be required for its differentiation (e.g. bld genes for aerial growth and whi genes for sporulation) and antibiotics production (including actII-orf, redD, cdaR as pathway-specific regulatory genes and afsR, absA1/A2 as pleiotropic regulatory genes). Streptomyces are Gram-positive eubacteria that are the major natural source of antibiotics, producing about half of all known microbial antibiotics [1] This genus has a complex life cycle, in which spores germinate to form a substrate mycelium of branching hyphae on solid (page number not for citation purposes). 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]. Several key genes affecting apical growth, chromosome segregation and cell division (e.g. divIVA, sffA, ftsZ, ftsQ, ftsK and parA/B; [11,12,13,14,15,16,17]) have been identified

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