New insights into regulation of specialized metabolism of Streptomyces viridosporus ATCC14672

Aim. Streptomyces viridosporus ATCC14672 produces moenomycins (MOE), direct nanomolar inhibitors of bacterial peptidoglycan glycosyltransferases. Low MOE titers complicate their scaled-up purification, blurring MOE translational prospects. We took genetic approach to interrogate the involvement of several well-known pleiotropic regulators in MOE biosynthesis. Methods. Bacterial genetics and bioassays were combined to generate recombinant strains harboring additional copies of selected genes, and to assess their effects on MOE production. Results. The promoters of MOE biosynthetic genes harbor operators for pleiotropic transcriptional factors. We show here that, out of several tested regulatory genes, bldD is able to activate the production of unknown antibiotic in MOE-deficient mutant, dO5, whereas in ATCC14672 total antibiotic activity dropped in response to bldD. The dominant-negative allele of lsr2 positively impacted antibiotic activity in ATCC14672 and dO5. We also tested the effects of several broad-specificity transporter genes on dO5. Conclusions. Our study adds new players to the network of genes impacting MOE production. S. viridosporus, under certain conditions, is capable of producing an unknown antibiotic, whose elimination might be tested to improve MOE titers.