The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2)

• Published in: Microbiology (Society for General Microbiology) Vol. 163; no. 10; pp. 1415 - 1419
• Main Authors: Som, Nicolle F, Heine, Daniel, Holmes, Neil, Knowles, Felicity, Chandra, Govind, Seipke, Ryan F, Hoskisson, Paul A, Wilkinson, Barrie, Hutchings, Matthew I
• Format: Journal Article
• Language: English
• Published: England Microbiology Society 01.10.2017
• Subjects: Anti-Bacterial Agents - biosynthesis; Anti-Bacterial Agents - chemistry; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Chromatography, High Pressure Liquid; Drug Resistance, Microbial - genetics; Gene Expression Regulation, Bacterial; Multigene Family; Mutation; Secondary Metabolism - genetics; Short Communication; Spores, Bacterial; Streptomyces coelicolor - physiology; Streptomyces; cryptic gene clusters; antibiotics; sporulation
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/mic.0.000524

MtrAB is a highly conserved two-component system implicated in the regulation of cell division in the Actinobacteria. It coordinates DNA replication with cell division in the unicellular Mycobacterium tuberculosis and links antibiotic production to sporulation in the filamentous Streptomyces venezuelae. Chloramphenicol biosynthesis is directly regulated by MtrA in S. venezuelae and deletion of mtrB constitutively activates MtrA and results in constitutive over-production of chloramphenicol. Here we report that in Streptomyces coelicolor, MtrA binds to sites upstream of developmental genes and the genes encoding ActII-1, ActII-4 and RedZ, which are cluster-situated regulators of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red). Consistent with this, deletion of mtrB switches on the production of Act, Red and streptorubin B, a product of the Red pathway. Thus, we propose that MtrA is a key regulator that links antibiotic production to development and can be used to upregulate antibiotic production in distantly related streptomycetes.