Figure 1

The proposed pathways of C. burnetii for virenose biosynthesis. The pathway might begin with either fructose-6-phosphate (1) glucose-6-phosphate (2) or mannose-6-phosphate (3). The hexose-6-phosphates are then converted to either glucose-1-phosphate (4) or manose-1-phosphate (5) respectively by a dual-specific α-D-phosphohexomutase. Next, thymidylyltransferase or guanylyltransferase generates dTDP-glucose (6) or GDP-mannose (7), respectively. The activated sugars are transformed to the common intermediates in the biosynthesis of deoxysugars dTDP-4-keto-6-deoxy-D-glucose (8) or GDP-4-keto-6-deoxy-D-mannose (9). The carbohydrates are then methylated at C3 by the product of the TylCIII gene yielding the corresponding intermediates (10, 11). Finally, the methylated TDP intermediate is reduced by a 4-ketoreductase to form TDP-D-virenose (12). In the GDP route the intermediate GDP-3-methyl-4-keto-6-deoxy-D-idose (11) is transformed by GDP-4-keto-6-deoxy-D-mannose epimerase/reductase to GDP-L-virenose (13) or it can be converted to GDP-D-virenose (15) by the activities of a 4-ketoreductase plus a 2-C’-epimerase.