Pyridinyl polythiazole class peptide antibiotic micrococcin P1 , secreted by foodborne Staphylococcus equorum WS2733, is biosynthesized nonribosomally

摘要: Recently, foodborne Staphylococcus equorum WS2733 was isolated from a French red smear cheese on account of its strong inhibitory activity against Gram-positive pathogens such as Listeria. The antagonistic substance identified macrocyclic peptide antibiotic micrococcin P1, which had previously not been reported for the genus Staphylococcus. Micrococcin also potent inhibitor malaria parasite Plasmodium falciparum, is structurally related to thiostrepton, thiocillins and nosiheptide. Although all these antibiotics have known quite long time, their mode biosynthesis determined in detail yet. By using degenerated PCR, gene fragment encoding nonribosomal synthetase (NRPS) could be amplified S. equorum. corresponding chromosomal locus disrupted by insertional mutagenesis, it shown that mutants obtained displayed P1-deficient phenotype. Sequence analysis coherent 2.8-kb revealed extensive homology NRPSs, allowed assignment domain organization ‘condensation-adenylation-thiolation-condensation’; an arrangement predicted only two loci within presumably 14-modular, 1.6-MDa biosynthetic NRPS template. Biochemical characterization adenylation exhibited selectivity substrate amino-acid threonine. All data substantiate biosynthesized nonribosomally, provide basis entire cluster. machinery will serve model system related, pharmacologically important pyridinyl polythiazole class antibiotics. Furthermore, this knowledge enable manipulation template, turn may grant targeted engineering even more anti-listerial anti-malaria drugs.