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Identification of a regulatory cascade that activates chloramphenicol biosynthesis in Streptomyces venezuelae

ABSTRACT: Specialised metabolites made by the genus Streptomyces form the basis of 55% of clinically used antibiotics as well as cancer therapeutics, immunosuppressants and other anti-infectives. 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 chloramphenicol biosynthesis is controlled by a regulatory cascade involving the developmental transcription factors OrrA, WblA and AdpA. OrrA directly activates the production of the WhiB-family protein WblA which binds to 90 target gene promoters, including adpA. AdpA is a pleiotropic regulator that directly activates chloramphenicol biosynthesis, and we propose that deletion of orrA or wblA results in an increase in the levels of AdpA which in turn leads to the increase in chloramphenicol biosynthesis observed in these mutants.

INSTRUMENT(S):

ORGANISM(S): Streptomyces Venezuelae

TISSUE(S): Cell Culture

SUBMITTER: Gerhard Saalbach

LAB HEAD: Matt Hutchings

PROVIDER: PXD064843 | Pride | 2026-05-21

REPOSITORIES: Pride

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