Network Mechanisms of Phosphate Control of Primary and Secondary Metabolism
Juan F. Martín, Alberto Sola-Landa, Fernando Santos-Beneit and Antonio Rodríguez-García
from: Streptomyces: Molecular Biology and Biotechnology (Edited by: Paul Dyson). Caister Academic Press, U.K. (2011)
The biosynthesis of hundreds of antibiotics and other secondary metabolites is repressed by inorganic phosphate, in spite of the fact that those metabolites are synthesized by quite different pathways. Derepression of many antibiotic biosynthesis genes occurs when the concentration of inorganic phosphate becomes limiting for growth. Phosphate control of primary and secondary metabolism in Streptomyces species is mediated by the two component system PhoR-PhoP. The genes under direct control of PhoP (the pho regulon) have been identified in S. coelicolor. They are involved in a variety of cellular functions, most notably in phosphate scavenging and phosphate transport. Phosphate control of secondary metabolism genes is not exerted by direct binding of PhoP to the promoters of those genes. Rather, PhoP controls directly other intermediate regulators in a regulatory cascade that in turn modulate expression of pathway-specific regulators. Indeed PhoP regulates expression of afsS in S. coelicolor that in turn triggers expression of actII-ORF4 and redD controlling actinorhodin and undecylprodigiosin biosynthesis. PhoP binds to a PHO box in the afsS promoter that overlaps with the AfsR binding sequence. Phosphate control also interacts with nitrogen regulation. PhoP binds to the promoters of glnR, glnA and other key genes of the nitrogen metabolism. This article provides new insights into the mechanisms underlying systems biology in Streptomyces read more ...