unidentified protein catalyzes the selective oxidation of the benzene (as shown in Fig. 2). Upon oxidation this intermediate will spontaneously lactonize to form the aromatic ring B and lose NovH in the process. The biosynthesis of L-noviose (ring C) is shown in Fig. 3. This process starts from glucose-1-phosphate where NovV takes dTTP and replaces the phosphate group with a dTDP group. NovT then oxidizes the 4-hydroxy group using NAD+. NovT also accomplishes a dehydroxylation of the 6 position of the sugar. NovW then epimerizes the 3 position of the sugar. The methylation of the 5 position is accomplished by NovU and S-adenosyl methionine (SAM). Finally NovS reduces the 4 position again to achieve epimerization of that position from the starting glucose-1-phosphate using NADH. Rings A, B, and C are coupled together and modified to give the finished novobiocin molecule. Rings A and B are coupled together by the enzyme NovL using ATP to diphosphorylate the carboxylate group of ring A so that the carbonyl can be attacked by the amine group on ring B. The resulting compound is methylated by NovO and SAM prior to glycosylation. NovM adds ring C (L-noviose) to the hydroxyl group derived from tyrosine with the loss of dTDP. Another methylation is accomplished by NovP and SAM at the 4 position of the L-noviose sugar. This methylation allows NovN to carbamylate the 3 position of the sugar as shown in Fig. 4 completing the biosynthesis of novobiocin. References External links Novobiocin bound to proteins in the PDB Antibiotics Coumarin drugs Benzamides Carbamates Topoisomerase inhibitors