Metabolomic investigation of the pseudouridimycin producer, a prolific streptomycete

Abstract

We report a metabolomic analysis of Streptomyces sp. ID38640, a soil isolate that produces the bacterial RNA polymerase inhibitor pseudouridimycin. The analysis was performed on the wild type and on ten different pum mutants blocked at different steps in pseudouridimycin biosynthesis. The results indicate that Streptomyces sp. ID38640 is able to produce, in addition to pseudouridimcyin, lydicamycins and deferroxiamines, as previously reported, also the lassopeptide ulleungdin, the non-ribosomal peptide antipain and the osmoprotectant ectoine. The corresponding biosynthetic gene clusters were readily identified in the strain genome. We also detected the known compound pyridindolol, for which we propose a previously unreported biosynthetic gene cluster, as well as three families of unknown metabolites. Remarkably, the levels of the different metabolites varied strongly in the different mutant strains, allowing detection of metabolites not normally seen in the wild type. Three newly constructed pum mutants, along with systematic investigation of the accumulated metabolites, shed further lights on pseudouridimycin biosynthesis. We also show that several Streptomyces strains, harboring the pum biosynthetic gene cluster and unrelated to ID38640, readily produce pseudouridimycin.