Sorbitol-6-phosphate dehydrogenase (S6PDH) (S6PDH)

Sorbitol-6-phosphate dehydrogenase (S6PDH) is a bacterial enzyme, typically encoded by the srlD gene, that plays a critical role in the phosphotransferase system (PTS)-mediated metabolism of sorbitol (UniProt: P0A9S1). It catalyzes the NAD+-dependent oxidation of D-sorbitol-6-phosphate to D-fructose-6-phosphate, which then enters the glycolytic pathway (EC 1.1.1.140). This enzyme is particularly significant in oral pathogens like Streptococcus mutans, where it enables the fermentation of sorbitol—a common sugar substitute—thereby contributing to acid production and dental caries (PubMed: 15252018). Because S6PDH is essential for bacterial growth on sorbitol and lacks a direct human ortholog (human sorbitol dehydrogenase does not require phosphorylation), it represents a potential target for narrow-spectrum antimicrobial agents (PubMed: 21673631). Inhibiting this enzyme could disrupt the metabolic flexibility of pathogens in sorbitol-rich environments, such as the human gut or oral cavity. Furthermore, S6PDH belongs to the short-chain dehydrogenase/reductase (SDR) family, characterized by a conserved Rossmann fold for nucleotide binding. Research into S6PDH inhibitors aims to reduce the cariogenic potential of dental biofilms without broadly affecting the systemic microbiome.

Other names

D-sorbitol-6-phosphate dehydrogenaseSrlDGlucitol-6-phosphate dehydrogenaseSorbitol-6-phosphate 2-dehydrogenaseKetose-6-phosphate reductase

Inhibition of the catalytic conversion of D-sorbitol-6-phosphate to D-fructose-6-phosphate, thereby blocking the entry of sorbitol into the glycolytic pathway.