Influence of Glyoxylate and Allantoin Pathways on Polyketide Production in Streptomyces coelicolor

JUAN PABLO MACAGNO, HUGO GRAMAJO, AND EDUARDO J. RODRIGUEZ

Mar del Plata, Argentina

Congreso; XLIII Reunion Anual de la Sociedad Argentina de Investigadores en Bioquímica y Biología Molecular (SAIB); 2007

In Streptomyces sp. acetyl-CoA is a key metabolite in the interaction between primary and secondary metabolism since it can be incorporated into celular structures and also is a precursor of polyketide antibiotics. In this work we have identified and characterized the components of the glyoxylate and allantoin pathways from S. coelicolor. Two clusters of putative genes involved in these pathways have been identified in the genome: sco0982 and sco0983 genes encoding isocitrate lyase and malate synthase are next to sco0981 which encodes a putative protein homologue to RamB, a negative regulator of acetate metabolism in C. glutamicum; sco6243, sco6247 y sco6248 genes encoding proteins involved in allantoin pathway are next to sco6246 which encodes a protein homologue to AllR, the allantoin regulator of E. coli. Genetic studies with mutant strains in each of these genes demonstrated that desregulation of these pathways strongly affect antibiotic production. These results could suggest that availability of precursors is a check point for the production of secondary metabolites. Enzyme activity profiles have been characterized to confirm the role of putative regulator proteins in each metabolic pathway. These studies will allow us to understand how enzymes involved in the primary metabolism affect the production of secondary metabolites in S. coelicolor.