Dietary sucrose is a major contributor to pathogenicity of oral bacteria. For example, in the etiology of dental caries : (1) sucrose provides the building blocks for synthesis of glycans that facilitate adherence of Streptococcal species to the tooth surface, and (2) bacterial fermentation of the sugar generates lactic acid that causes demineralization of tooth enamel. Sucrose itself comprises glucose and fructose molecules that are linked between carbon atom 1 of the former and carbon atom 2 of the latter. Sucrose is phosphorylated simultaneously with transport into the bacteria, where it is subsequently hydrolyzed by an enzyme designated sucrose 6-phosphate hydrolase (S6PH). Alternate linkages between C1 of glucose and the remaining five carbon atoms of fructose yield five analogs of sucrose designated trehalulose (1-1), turanose (1-3), maltulose (1-4), leucrose (1-5) and palatinose (1-6). Remarkably, these isomeric compounds (in contrast to the natural disaccharide) do not support growth of oral streptococci. Importantly, two of these relatively sweet analogs, palatinose and leucrose, are produced on an industrial scale and - by virtue of their non-cariogenicity - are potential substitutes for dietary sucrose. Why organisms such as Streptococcus mutans fail to metabolize the sucrose isomers has never been established, and is a topic that we have recently addressed. Two major accomplishments of the past year include the first biosynthesis of all five phosphorylated isomers of sucrose, and the demonstration that S6PH is unable to catalyze the hydrolysis of any of these phosphorylated derivatives. It is our contention that subtle conformational differences, between the compact globular sucrose molecule and the linearly extended forms of the isomers, are the basis for substrate discrimination by S6PH. By corollary, our findings provide insight to the rational synthesis of sucrose analogs that - by inactivating S6PH - may permit selective targeting and inhibition of growth of caries-inducing bacteria.
