title: An orphan histidine kinase, OhkA, regulates both secondary metabolism and morphological differentiation in Streptomyces coelicolor.
abstract: We report here the physiological and genetic characterization of an orphan histidine kinase (HK) (OhkA, SCO1596) in Streptomyces coelicolor and its homolog (OhkAsav, SAV_6741) in Streptomyces avermitilis. The physiological analysis showed that the ohkA mutant of S. coelicolor exhibits impaired aerial mycelium formation and sporulation and overproduction of multiple antibiotics on mannitol-soy flour (MS) medium, especially actinorhodin (ACT) and calcium-dependent antibiotic (CDA), and disruption of ohkAsav in S. avermitilis also led to the similar phenotypes of impaired morphological differentiation and significantly increased oligomycin A production. DNA microarray analysis combined with real-time reverse transcription-PCR (RT-PCR) and RNA dot blot assay in the S. coelicolor ohkA deletion mutant confirmed the physiological results by showing the upregulation of genes involved in the biosynthesis of ACT, CDA, undecylprodigiosin (RED), a yellow type I polyketide (CPK, SCO6273-6289), and a sesquiterpene antibiotic, albaflavenone (SCO5222-5223). The results also suggested that the increased production of ACT and RED in the mutant could be partly ascribed to the enhanced precursor malonyl coenzyme A (malonyl-CoA) supply through increased transcription of genes encoding acetyl-CoA carboxylase (ACCase). Interestingly, DNA microarray analysis also showed that deletion of ohkA greatly downregulated the transcription of chpABCDEFGH genes essential for aerial mycelium formation by S. coelicolor on MS medium but significantly increased transcription of ramS/C/R, which is responsible for SapB formation and regulation and is normally absent on MS medium. Moreover, many other genes involved in development, such as bldM/N, whiG/H/I, ssgA/B/E/G/R, and whiE, were also significantly downregulated upon ohkA deletion. The results clearly demonstrated that OhkA is an important global regulator for both morphological differentiation and secondary metabolism in S. coelicolor and S. avermitilis.
authors.affiliation: Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, People's Republic of China.
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Lu
authors.forename: Juanmei
authors.initials: J
authors.lastname: He
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Chen
authors.forename: Fujun
authors.initials: F
authors.lastname: Dang
authors.forename: Weiwen
authors.initials: W
authors.lastname: Zhang
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
authors.forename: Weihong
authors.initials: W
authors.lastname: Jiang
mesh_terms: D004734:Energy Metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D016680:Genome, Bacterial; D000071677:Histidine Kinase; D016297:Mutagenesis, Site-Directed; D020411:Oligonucleotide Array Sequence Analysis; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D013171:Spores, Bacterial / Q000502:physiology; D048372:Streptomyces coelicolor / Q000201:enzymology* / Q000378:metabolism
chemical_list: D011494:Protein Kinases; D000071677:Histidine Kinase