Allantoin catabolism influences the production of antibiotics in Streptomyces coelicolor

LAURA NAVONE; PAULA CASATI; CUAUHTÉMOC LICONA-CASSANI; ESTEBAN MARCELLIN; LARS K. NIELSEN; EDUARDO JOSE RODRIGUEZ; HUGO GRAMAJO

Applied Microbiology and Biotechnology

Springer

Año: 2014 vol. 98 p. 351 - 360

1432-0614

Purines are a primary source of carbon and nitrogenin soil; however, their metabolism is poorly understood inStreptomyces. Using a combination of proteomics, metabolomics,and metabolic engineering, we characterized the allantoinpathway in Streptomyces coelicolor. When cells grew inglucose minimal medium with allantoin as the sole nitrogensource, quantitative proteomics identified 38 enzymes upregulatedand 28 downregulated. This allowed identifying sixnew functional enzymes involved in allantoin metabolism inS. coelicolor. Fromthose, using a combination of biochemicaland genetic engineering tools, it was found that allantoinase(EC 3.5.2.5) and allantoicase (EC 3.5.3.4) are essential forallantoin metabolism in S. coelicolor. Metabolomics showedthat under these growth conditions, there is a significantintracellular accumulation of urea and amino acids, whicheventually results in urea and ammonium release into theculture medium. Antibiotic production of a urease mutantstrain showed that the catabolism of allantoin, and the subsequentrelease of ammonium, inhibits antibiotic production.These observations link the antibiotic production impairmentwith an imbalance in nitrogen metabolism and provide thefirst evidence of an interaction between purine metabolismand antibiotic biosynthesis.