PT - JOURNAL ARTICLE AU - Nicolle F. Som AU - Daniel Heine AU - John T. Munnoch AU - Neil A. Holmes AU - Felicity Knowles AU - Govind Chandra AU - Ryan F. Seipke AU - Paul A. Hoskisson AU - Barrie Wilkinson AU - Matthew I Hutchings TI - MtrA is an essential regulator that coordinates antibiotic production and development in <em>Streptomyces</em> species AID - 10.1101/090399 DP - 2016 Jan 01 TA - bioRxiv PG - 090399 4099 - http://biorxiv.org/content/early/2016/12/05/090399.short 4100 - http://biorxiv.org/content/early/2016/12/05/090399.full AB - Streptomyces bacteria make numerous secondary metabolites, including half of all known antibiotics. Production is coordinated with their complex life cycles but the regulators that coordinate development with antibiotic biosynthesis are largely unknown. This is important to understand because most Streptomyces secondary metabolites are not produced under laboratory conditions and unlocking the ‘cryptic’ biosynthetic gene clusters (BGCs) is a major focus for antibiotic discovery. Here we characterise the highly conserved actinobacterial response regulator MtrA in Streptomyces species. MtrA is essential and regulates cell cycle progression in Mycobacterium tuberculosis. We show that MtrA is also essential in Streptomyces venezuelae where it controls genes required for DNA replication and cell division. MtrA also directly regulates the expression of genes in &gt;70% of its BGCs and artificially activating MtrA switches on the production of antibiotics in S. coelicolor and S. venezuelae. We propose that MtrA coordinates antibiotic production and development in Streptomyces species.