ROLE OF MALIC ENZYME IN THE METABOLISM OF Streptomyces coelicolor

LAURA NAVONE; PAULA CASATI; HUGO GRAMAJO; EDUARDO JOSE RODRIGUEZ

Puerto Madryn

Congreso; 46 Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2010

Sociedad Argentina de Bioquímica y Biología Vegetal

Antibiotics are products of secondary metabolism and are veryimportant for human health. Soil bacteria Streptomyces produce80% of total known antibiotics. A lot of effort has been made tounderstand biosynthesis and regulation of secondary metabolism inthis genus. However, little attention has been paid to the centralmetabolic network which supplies building blocks for antibioticbiosynthesis.Anaplerotic enzymes are very important in cell metabolismbecause they interconnect the main metabolic pathways. Inprevious work we characterized a NAD and a NADP dependentmalic enzyme from S. coelicolor, these enzymes catalyze theoxidative decarboxylation of L-malate into pyruvate with reductionof NAD or NADP. Individual mutations in genes encoding for theseenzymes resulted in no significant phenotype, however the doublemutant strain showed a pronounced decrease in antibiotic andtriacylglycerol production under different carbon sources tested.Metabolites analysis evidenced accumulation of TCA-precursorsin the doble mutant but no differences in acetyl-CoA levels. Theseresults indicate that these anaplerotic enzymes play an importantrole connecting energy-producing and biosynthetic pathways attransition phase between primary and secondary metabolism inStreptomyces. How the bacterium senses changes in metabolismand modifies the regulation of antibiotic production is under study.