Role of Malic enzyme in the metabolism of Streptomyces coelicolor

NAVONE L, CASATI P, GRAMAJO H, RODRIGUEZ E.

Puerto Madryn

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigadores en Bioquímica y Biología Molecular (SAIB); 2010

Antibiotics are products of secondary metabolism and are very important for human health, soil bacteria Streptomyces produce 80% of total known antibiotics. A lot of effort has been made to understand biosynthesis and regulation of secondary metabolism in this genus. However, little attention has been paid to the central metabolic network which supplies building blocks for antibiotic biosynthesis. Anaplerotic enzymes are very important in cell metabolism because they interconnect the main metabolic pathways. In previous work we characterized a NAD and a NADP dependent malic enzyme from S. coelicolor, these enzymes catalyze the oxidative decarboxylation of L-malate into pyruvate with reduction of NAD or NADP. Individual mutations in genes encoding for these enzymes resulted in no significant phenotype, however the double mutant strain showed a pronounced decrease in antibiotic and triacylglycerol production under different carbon sources tested. Metabolites analysis evidenced accumulation of TCA-precursors in the doble mutant but no differences in acetyl-CoA levels. How the bacterium senses changes in metabolism and modifies the regulation of antibiotic production is under study. These results indicate that these anaplerotic enzymes play an important role connecting energy-producing and biosynthetic pathways at transition phase between primary and secondary metabolism in Streptomyces.