viomycin

Viomycin is a member of the tuberactinomycin family, a group of nonribosomal peptide antibiotics exhibiting anti-tuberculosis activity. The tuberactinomycin family is an essential component in the drug cocktail currently used to fight infections of Mycobacterium tuberculosis. Viomycin was the first member of the tuberactinomycins to be isolated and identified, and was used to treat TB until it was replaced by the less toxic, but structurally related compound, capreomycin. The tuberactinomycins target bacterial ribosomes, binding RNA and disrupting bacterial protein synthesis and certain forms of RNA splicing. Viomycin is produced by the actinomycete Streptomyces puniceus.

== Biosynthesis== The gene cluster for viomycin has been sequenced from Streptomyces sp. strain ATCC 11861, Streptomyces vinaceus and from Streptomyces lividans 1326. It consists of a central cyclic pentapeptide code assembled from nonribosomal peptide synthetase (NRPS). The NRPS contains 4 proteins: VioA, VioF, VioI, and VioG. These proteins condense and cyclize two molecules of L-2,3-diaminopropionate (L-Dap), two molecules of L-serine (L-Ser), and one molecule of (2S,3R)-capreomycidine (L-Cam). After cyclizing these, VioJ catalyzes the α,β-desaturation of this preliminary structure. It is proposed that the viomycin gene cluster includes 36.3 kb of contiguous DNA that encodes 20 open reading frames (ORFs) that are involved in the biosynthesis, regulation, and eventual activation viomycin. In addition to these ORFs, the structure contains the resistance gene vph. The following is a summary of the ORFs and their functions. VioA: NRPS (A-PCP-C-A-PCP-C) VioH: Type II thioesterase VioO: NRPS (A-PCP)-β-lysine activation VioB: 2,3-diaminopropionate synthase VioI: NRPS (PCP-C) VioP: Lysine 2,3-aminomutase VioC: L-Arg hydroxylase VIoJ: 2,3-diaminopropionyl α,β-desaturase vph: Viomycin phosphotransferase VioD: Capreomycidine synthase VioK: Ornithine cyclodeaminase VioQ: Capreomycidine hydroxylase VioE: Permease VioL: Carbamoyltransferase VioR: Transcriptional regulator VioF: NRPS (A-PCP-C) VIoM: NRPS (C)-β-lysine transferase VIoS: Viomycin-phosphate phosphatase VioG: NRPS (A-PCP-C/) VioN: MbtH homolog VioT: Transcriptional regulator