The enzymes OxyA, OxyB, OxyC, and OxyD are cytochrome P450 enzymes. OxyB catalyzes oxidative cross-linking between residues 4 and 6, OxyA between residues 2 and 4, and OxyC between residues 5 and 7. This cross-linking occurs while the heptapeptide is covalently bound to the PCP domain of the 7th NRPS module. These P450s are recruited by the X domain present in the 7th NRPS module, which is unique to glycopeptide antibiotic biosynthesis. The cross-linked heptapeptide is then released by the action of the TE domain, and methyltransferase Vmt then N-methylates the terminal leucine residue. GtfE then joins D-glucose to the phenolic oxygen of residue 4, followed by the addition of vancosamine catalyzed by GtfD. Some of the glycosyltransferases capable of glycosylating vancomycin and related nonribosomal peptides display notable permissivity and have been employed for generating libraries of differentially glycosylated analogs through a process known as glycorandomization. Total synthesis
Both the vancomycin aglycone and the complete vancomycin molecule have been targets successfully reached by total synthesis. The target was first achieved by David Evans in October 1998, KC Nicolaou in December 1998, Dale Boger in 1999, and has recently been more selectively synthesized again by Dale Boger in 2020. Pharmacology and chemistry
Vancomycin is a branched tricyclic glycosylated nonribosomal peptide produced by the Actinomycetota species Amycolatopsis orientalis (formerly designated Nocardia orientalis). Vancomycin exhibits atropisomerism — it has multiple chemically distinct rotamers owing to the rotational restriction of some of the bonds. The form present in the drug is the thermodynamically more stable conformer.
Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also taken by mouth as a treatment for severe Clostridium difficile colitis. When taken by mouth it is poorly absorbed.Common side effects include pain in the area of injection and allergic reactions. Occasionally, hearing loss, low blood pressure, or bone marrow suppression occur. Safety in pregnancy is not clear, but no evidence of harm has been found, and it is likely safe for use when breastfeeding. It is a type of glycopeptide antibiotic and works by blocking the construction of a cell wall.Vancomycin was approved for medical use in the United States in 1958. It is on the World Health Organizations List of Essential Medicines. The World Health Organization classifies vancomycin as critically important for human medicine. It is available as a generic medication. Vancomycin is made by the soil bacterium Amycolatopsis orientalis. Medical uses
Vancomycin is indicated for the treatment of serious, life-threatening infections by Gram-positive bacteria unresponsive to other antibiotics. The increasing emergence of vancomycin-resistant enterococci has resulted in the development of guidelines for use by the Centers for Disease Control Hospital Infection Control Practices Advisory Committee.