Undecaprenyl Pyrophosphate Synthase (UPPS) is a critical enzyme in the production of complex bacterial polysaccharides crucial for the survival of most bacteria. However, these polysaccharides are also crucial for the survival of many symbiotic and benign microbes. Our interest is in developing routes to affect the activity of UPPS from harmful bacteria without affecting UPPS from other organisms. In order to target pathogens over benign and symbiotic species, differences in the structure of UPPS and the enzyme-substrate interactions can be probed using analogues of the native substrate Farnesyl Diphosphate (FPP). Three sets of photoactive analogues have been synthesized to study how UPPS interacts with substrates that differ in either sterics, polarity or electrostatics. Enzymatic characterization with UPPS from three species of bacteriahas been performed with each of eight FPP analogues. Differences in activity have been identified using a high performance liquid chromatography and new 96-well plate-based fluorescence assay. By further understanding the enzyme selectivity between different organisms, certain analogue characteristics have been exploited to target one bacterial species over another.

Substrate specificity of undecaprenyl pyrophosphate synthase as potential antibacterial target

247th National Meeting (2014)

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