dTDP-glucose 4,6-dehydratase (RmlB)

dTDP-glucose 4,6-dehydratase (RmlB) is an NAD+-dependent enzyme that catalyzes the conversion of dTDP-glucose to dTDP-4-dehydro-6-deoxy-D-glucose through a three-step process: oxidation, dehydration, and reduction[1][2][3][8][9]. This is the second committed step in the dTDP-L-rhamnose biosynthetic pathway, which is vital for the production of L-rhamnose, an essential component of the cell wall in many pathogenic bacteria[1][5]. The enzyme is a homodimer, structurally characterized by a Rossmann fold and is considered a member of the short-chain dehydrogenase/reductase (SDR) family[1][5]. As the dTDP-L-rhamnose pathway is absent in humans, RmlB is a potential target for developing new antibiotics, as its inhibition can impair bacterial viability without affecting human cells[5][3]. Alternative names include TDP-glucose oxidoreductase, RfbB, and DESIV, and similar enzymes are found across various pathogenic bacterial species[1][3][5][8][9].

Other names

Thymidine diphosphoglucose oxidoreductaseTDP-glucose oxidoreductasedTDP-glucose 4,6-hydro-lyaseDESIVRfbB (in some species, e.g., Bacillus anthracis)

Inhibition of dTDP-glucose 4,6-dehydratase would block dTDP-L-rhamnose biosynthesis, disrupting bacterial cell wall formation and inhibiting bacterial growth[5][3].