Streptomyces bacteria make numerous secondary metabolites, including half of all 25 known antibiotics. Production is coordinated with their complex life cycles but the regulators 26 that coordinate development with antibiotic biosynthesis are largely unknown. This is 27 important to understand because most Streptomyces secondary metabolites are not produced 28 under laboratory conditions and unlocking the 'cryptic' biosynthetic gene clusters (BGCs) is a 29 major focus for antibiotic discovery. Here we characterise the highly conserved actinobacterial 30 response regulator MtrA in Streptomyces species. MtrA is essential and regulates cell cycle 31 progression in Mycobacterium tuberculosis. We show that MtrA is also essential in 32 Streptomyces venezuelae where it controls genes required for DNA replication and cell 33 division. MtrA also directly regulates the expression of genes in >70% of its BGCs and 34 artificially activating MtrA switches on the production of antibiotics in S. coelicolor and S.

We report the genome sequence of Streptomyces goldiniensis ATCC 21386, a strain which produces the anti-bacterial and anti-virulence polyketide, aurodox. The genome of S. goldiniensis ATCC 21386 was sequenced using a multiplatform hybrid approach, revealing a linear genome of ~10 Mbp with a G+C content of 71 %. The genome sequence revealed 36 putative biosynthetic gene clusters (BGCs), including a large region of 271 Kbp that was rich in biosynthetic capability. The genome sequence is deposited in DDBJ/EMBL/GenBank with the accession number PRJNA602141.