Web supplement

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"Cross-regulation among disparate antibiotic biosynthetic pathways of Streptomyces coelicolor". Jianqiang Huang, Jing Shi, Virginie Molle, Bjorn Sohlberg, David Weaver, Maureen J. Bibb, Nitsara Karoonuthaisiri, Chih-Jian Lih, Camilla M. Kao, Mark J. Buttner, Stanley N. Cohen

published in

Molecular Microbiology, Vol. 58, Issue 5, pp. 1276-1287, December 2005.

A complex program of regulation governs gene expression during development of the morphologically and biochemically complex eubacterial genus Streptomyces. Earlier work has suggested a model in which "higher level" pleiotropic regulators activate "pathway-specific" regulators located within chromosomal gene clusters encoding individual antibiotics. We used mutational analysis and adventitious overexpression of key S. coelicolor regulators to investigate functional interactions among them. We report here that cluster-situated regulators (CSRs) thought to be pathway-specific can also control other antibiotic biosynthetic gene clusters, and thus have pleiotropic actions. Surprisingly, we also find that CSRs exhibit growth-phase-dependent control over afsR2/afsS, a "higher level" pleiotropic regulatory locus not located within any of the chromosomal gene clusters it targets, and further demonstrate that cross regulation by CSRs is modulated globally and differentially during the S. coelicolor growth cycle by the RNaseIII homolog AbsB. Our results, which reveal a network of functional interactions among regulators that govern production of antibiotics and other secondary metabolites in S. coelicolor, suggest that revision of the currently prevalent view of higher-level vs. pathway-specific regulation of secondary metabolism in Streptomyces species is warranted.

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Last updated: December 2, 2005