Identification of the gene cluster for the dithiolopyrrolone antibiotic holomycin in Streptomyces clavuligerus.

ABSTRACT: Streptomyces clavuligerus, an industrially important producer of clavulanate as well as cephem antibiotics, also produces the N-acylated dithiolopyrrolone antibiotic holomycin, a reported inhibitor of RNA synthesis. The genome sequence of S. clavuligerus ATCC 27064 was examined for a potential biosynthetic gene cluster, assuming that holomycin arises from some derivative of an L-Cys-L-Cys dipeptide that has undergone eight-electron oxidation, fused five-five ring formation, and decarboxylation. ORFs 3483-3492 comprise a candidate cluster, with a predicted acyltransferase, a stand-alone nonribosomal peptide synthetase (NRPS) module, and four flavin-dependent oxidoreductases. Deletions of ORF3488, the NRPS module, and ORF3489, a phosphopantothenoylcysteine decarboxylase homolog, abolished ho

SUBMITTER: Li B 

PROVIDER: S-EPMC2993409 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature