CARB 85 |
| A pathway has been proposed for the biosynthesis of noviose, the sugar component of the Streptomyces spheroides DNA gyrase-inhibiting antibiotic novobiocin. NovW, which is thought to serve as a dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase, has high sequence homology to the validated 3,5-epimerase RmlC from the dTDP-L-rhamnose pathway and to the 5-epimerase EvaD from the dTDP-epivancosamine pathway. Sequence-wise, NovW is more like Mycobacterium tuberculosis 3,5-epimerase RmlC than the M. tb enzyme is to some other authenticated RmlC proteins. A combination of structural studies, solvent isotope incorporation and kinetic analyses has been employed to establish the true activity of NovW. Comparison of the sequences, structures and the activities of NovW, EvaD and RmlC has been made in order to define features required for 3- (NovW), 5- (EvaD) or 3,5-epimerisation (RmlC). The data to hand highlight the need for caution when assigning function based solely on gene sequence similarities and/or protein crystal structure data. |
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General Papers: Analytical Chemistry and Biochemistry of Carbohydrates and Derivatives
8:30 AM-12:30 PM, Thursday, 30 March 2006 Georgia World Congress Center -- B409, Oral
Division of Carbohydrate Chemistry |