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

Som, Nicolle F. and Heine, Daniel and Holmes, Neil and Knowles, Felicity and Chandra, Govind and Seipke, Ryan F. and Hoskisson, Paul A and Wilkinson, Barrie and Hutchings, Matthew I. (2017) The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2). Microbiology, 163 (10). pp. 1415-1419. ISSN 1465-2080 (https://doi.org/10.1099/mic.0.000524)

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Abstract

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.

ORCID iDs

Som, Nicolle F., Heine, Daniel, Holmes, Neil, Knowles, Felicity, Chandra, Govind, Seipke, Ryan F., Hoskisson, Paul A ORCID logoORCID: https://orcid.org/0000-0003-4332-1640, Wilkinson, Barrie and Hutchings, Matthew I.;