title: Developmental defect of cytochrome oxidase mutants of Streptomyces coelicolor A3(2).
abstract: To study the link between energy metabolism and secondary metabolism/morphological development in Streptomyces, knockout mutants were generated with regard to the subunits of the cytochrome oxidase supercomplex (CcO) in Streptomyces coelicolor A3(2). All mutants exhibited an identical phenotype: viable but defective in antibiotic production and cell differentiation when grown in both complex and minimal media. The growth yield of the CcO mutant was about half of that of the WT strain on glucose medium while both strains grew similarly on maltose medium. Intracellular ATP measurement demonstrated that the CcO mutant exhibited high intracellular ATP level. A similar elevation of intracellular ATP level was observed with regard to the WT strain cultured in the presence of BCDA, a copper-chelating agent. Reverse transcriptase PCR analysis demonstrated that the transcription of ATP synthase operon is upregulated in the CcO mutant. Addition of carbonylcyanide m-chlorophenylhydrazone, an inhibitor of ATP synthesis, promoted antibiotic production and aerial mycelia formation in the CcO mutant and BCDA-treated WT cells. We hypothesize that the deficiency of CcO causes accumulation of intracellular ATP, and that the high ATP level inhibits the onset of development in S. coelicolor.
authors.affiliation: Life Science Research Center, College of Bioresource Sciences, Nihon University, 1866 Kameino, 252-0880 Fujisawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Life Science Research Center, College of Bioresource Sciences, Nihon University, 1866 Kameino, 252-0880 Fujisawa, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Chijiwa
authors.affiliation: Life Science Research Center, College of Bioresource Sciences, Nihon University, 1866 Kameino, 252-0880 Fujisawa, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nishiyama
authors.affiliation: Life Science Research Center, College of Bioresource Sciences, Nihon University, 1866 Kameino, 252-0880 Fujisawa, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takano
authors.affiliation: Life Science Research Center, College of Bioresource Sciences, Nihon University, 1866 Kameino, 252-0880 Fujisawa, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ueda
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D055786:Gene Knockout Techniques; D007211:Indoles / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000096:biosynthesis* / Q000235:genetics; D025282:Mycelium / Q000254:growth & development; D064210:Secondary Metabolism / Q000235:genetics; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000254:growth & development*
chemical_list: D007211:Indoles; C042610:5-bromo-4-chloroindoxyl acetate; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D025261:Mitochondrial Proton-Translocating ATPases