Roles of VioG and VioQ in the Incorporation and Modification of the Capreomycidine Residue in the Peptide Antibiotic Viomycin

The nonproteinogenic amino acid capreomycidine is the signature residue found in the tuberactinomycin family of antitubercular peptide antibiotics and an important element of the pharmacophore. Recombinant VioG, a single-module peptide synthetase from the viomycin gene cluster cloned from Streptomyces vinaceus (ATCC11861), specifically activates capreomycidine for incorporation into viomycin (tuberactinomycin B). Insertional disruption of the putative hydroxylase gene vioQ resulted in a mutant that accumulated tuberactinomycin O, suggesting that hydroxylation at C-5 of the capreomycidine residue is a post-assembly event. The inactivated chromosomal copy of vioQ could be complemented with a wild-type copy of the gene to restore viomycin production.