Biosynthesis of vancomycin: identification of TDP‐glucose: aglycosyl‐vancomycin glucosyltransferase from Amycolatopsis orientalis

An enzyme was identified from Amycolatopsis orientalis as TDP‐glucose:aglycosyl vancomycin glucosyltransferase. It catalyzes the addition of a sugar onto the peptide core of the antibiotic and will use TDP‐Glc, UDP‐Glc and UDP‐Gal as co‐substrates for the transferase reaction. The peptide core of the antibiotic must have a free hydroxyl group on ring B and a specific change in the conformation of the core eliminated activity of the enzyme. Enzyme activity was optimal at pH values between 9.0 and 10.0 and a temperature of 37°C. Under these conditions, the enzyme reaction is linear for one hour. Gel filtration studies demonstrated that all the enzyme activity eluted from the column at a molecular weight of 44 kDa. This is the first report of an enzyme activity that appears to be associated with the biosynthesis of glycopeptide antibiotics.