Biosynthesis of rubradirin as an ansamycin antibiotic from Streptomyces achromogenes var. rubradiris NRRL3061

Abstract

The four overlapping cosmids from the rubradirin producer, Streptomyces achromogenes var rubradiris NRRL 3061, have 58 ORFs within a 105.6 kb fragment. These ORFs harbored essential genes responsible for the formation and attachment of four distinct moieties, along with the genes associated with regulatory, resistance, and transport functions. The PKS (rubA) and glycosyltransferase (rubG2) genes were disrupted in order to demonstrate a complete elimination of rubradirin production. The rubradirin biosynthetic pathway was proposed based on the putative functions of the gene products, the functional identification of sugar genes, and the mutant strains.

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

“…The cluster encoding the formation of rubradirin, an unusual naphthalenic ansamycin includes homologs of all the rif AHBA genes except rifI. 52 The ansatrienin producer S. collinus gave two AHBA biosynthesis subclusters, one associated with other ansatrienin genes and containing all the genes found in the rif cluster except rifI. 53 The other is associated with some putative naphthomycin biosynthesis genes and contains homologs of all the rif AHBA genes except rifJ which, as in the rif case, may be located elsewhere among the naphthomycin biosynthesis genes.…”

A system for the targeted amplification of bacterial gene clusters multiplies antibiotic yield in Streptomyces coelicolor

“…A major group of secondary metabolites, the polyketides, have commercial importance or potential applications as antibacterials, antifungals, antiparasitics, animal growth promotants, or immunosuppressants (22). Polyketide biosynthetic pathways are encoded by clusters of genes ranging in size from around 20 kb to more than 100 kb (23). These observations suggest that controlled, stable amplification of entire antibiotic biosynthetic gene clusters would be a valuable and generally applicable tool for engineering highyielding production strains.…”

Nitrososynthase-Triggered Oxidative Carbon–Carbon Bond Cleavage in Baumycin Biosynthesis

“…9 Upon incubation of TDP- l - epi -vancosamine ( 4 ) with SAM and RubN7, we observed the formation of TDP- l -evernosamine ( 16 ). On further incubation with ORF36/DnmZ, the formation of TDP- l -evernitrosose ( 17 ) was observed and turnover with DnmZ reactions with TDP- l -evernitrosose were slower than with ORF36 (see Supplementary materials S9).…”

“…africana , which encodes a nitrososynthase catalyzing the oxidation of an amino sugar to its nitroso congener via two consecutive flavin-dependent monooxygenation reactions. 8 Analogous enzymes are found in the biosynthetic pathways of rubradirin 9 and kijanimicin 10 generating structurally similar nitrososugars. These nitrososugars then serve as the precursors for nitrosugar moieties in natural products of which they are constituents.…”

“…9,10,20 In our previous studies of nitrosugar formation in the everninomicin/rubradirin pathways, the nitrososynthase activity of ORF36/RubN8 was established using TDP- l - epi -vancosamine ( 4 ) as substrate, which is a biosynthetic precursor to the expected substrate TDP- l -evernosamine ( 16 ). We observed the oxime-aldehyde hydrated species ( 10 ) ( m/z = 576) but were unable to account for its structure in the context of nitrosugar formation.…”