RT Journal Article SR Electronic T1 MtrA is an essential regulator that coordinates antibiotic production and sporulation in Streptomyces species JF bioRxiv FD Cold Spring Harbor Laboratory SP 090399 DO 10.1101/090399 A1 Nicolle F. Som A1 Daniel Heine A1 John T. Munnoch A1 Neil A. Holmes A1 Felicity Knowles A1 Govind Chandra A1 Ryan F. Seipke A1 Paul A. Hoskisson A1 Barrie Wilkinson A1 Matthew I. Hutchings YR 2016 UL http://biorxiv.org/content/early/2016/12/12/090399.abstract AB Streptomyces bacteria make numerous secondary metabolites, including half of all known antibiotics. Understanding the global regulation of secondary metabolism is important because most Streptomyces natural products are not made under laboratory conditions and unlocking ‘cryptic’ biosynthetic gene clusters (BGCs) is a major focus for natural product discovery. Production is coordinated with sporulation but the regulators that coordinate development with antibiotic biosynthesis are largely unknown. Here we characterise a highly conserved actinobacterial response regulator called MtrA in antibiotic-producing Streptomyces species. We show that MtrA is an essential global regulator of secondary metabolism that directly activates antibiotic production in in S. coelicolor and S. venezuelae. MtrA also controls key developmental genes required for DNA replication and cell division and we propose that MtrA is the missing link that coordinates secondary metabolism with development in Streptomyces species.