biostudies-literatureMcLean TCBiotechnology and Biological Sciences Research Councile0299125https://www.ebi.ac.uk/biostudies/studies/S-EPMC12802291biostudies-literatureUnknown17(1)Streptomyces specialized metabolites account for over half of all clinically used antibiotics, as well as numerous antifungal, anticancer, and immunosuppressant agents. Two-component systems, which are widespread in bacteria, are key regulators of antibiotic production in Streptomyces species, yet their activating signals remain poorly understood. CutRS was the first two-component system identified in the genus Streptomyces, and deletion of cutRS in Streptomyces coelicolor was shown to enhance antibiotic production, although its CutR regulon does not include biosynthetic genes. Here, we used Streptomyces venezuelae NRRL B-65442 to further investigate CutRS function. We show that deletion of cutRS increases growth rate and a reversal of the gmBioThe conserved two-component systems CutRS and CssRS control the protein secretion stress response in Streptomyces.PMC12802291BB/X01097X/1BB/M011216/1BBS/E/J/000PR9790Martins CBatey SFDChandra GBeaton ADMMcLean TCSaalbach GChina JHutchings MIHolmes NAWilkinson BfalseThe conserved two-component systems CutRS and CssRS control the protein secretion stress response in Streptomyces.Streptomyces specialized metabolites account for over half of all clinically used antibiotics, as well as numerous antifungal, anticancer, and immunosuppressant agents. Two-component systems, which are widespread in bacteria, are key regulators of antibiotic production in Streptomyces species, yet their activating signals remain poorly understood. CutRS was the first two-component system identified in the genus Streptomyces, and deletion of cutRS in Streptomyces coelicolor was shown to enhance antibiotic production, although its CutR regulon does not include biosynthetic genes. Here, we used Streptomyces venezuelae NRRL B-65442 to further investigate CutRS function. We show that deletion of cutRS increases growth rate and a reversal of the g2026-01-01T00:00:00Z2026 Jan2026-06-11T04:57:35.947Z2026-06-11T03:08:14.6ZS-EPMC128022914139593910.1128/mbio.02991-25