Identification of the Streptomyces WblA regulon reveals drastic effects on development and specialized metabolism

Streptomyces venezuelae is a model for the genus because it is fast-growing, sporulates in liquid culture within 24 hours and coordinates production of the antibiotic chloramphenicol with sporulation. In this work we demonstrate that the conserved orphan response regulator OrrA directly controls the production of the conserved WhiB-like protein WblA which in turn binds to 90 target gene promoters, including genes required for aerial hyphae production and sporulation.

We provide evidence that WblA directly controls the production of AdpA and BldN, key developmental regulators that are required for entry into sporulation and show that the cellular levels of the key developmental regulators AdpA, BldM, BldN, RsbN, WhiA, WhiB and WhiD are significantly altered in a ∆wblA mutant. Proteins encoded by 32 of the 33 predicted specialised metabolite biosynthetic gene clusters in S. venezuelae are also significantly affected by loss of WblA and we show that the ∆wblA mutant over produces the antibiotic chloramphenicol.