Glycerol dehydratase (GDH)

Bacterial glycerol dehydratase (EC 4.2.1.30) is a coenzyme B12-dependent enzyme that catalyzes the dehydration of glycerol to 3-hydroxypropionaldehyde (3-HPA). This enzyme is primarily found in various anaerobic and facultative anaerobic bacteria, such as Klebsiella pneumoniae and Lactobacillus reuteri, where it plays a crucial role in glycerol fermentation (UniProt: P0A6F5). The product of this reaction, 3-HPA, is a precursor for 1,3-propanediol and also functions as a potent antimicrobial agent known as reuterin (PubMed: 10411744). In a clinical context, glycerol dehydratase is significant due to its role in the gut microbiome's ability to produce antimicrobial substances that inhibit the growth of pathogens. While not a traditional target for systemic drugs, it is a focus for probiotic research and metabolic engineering to modulate the microbial environment. The enzyme is characterized by a complex mechanism involving radical chemistry and is susceptible to mechanism-based inactivation, requiring specific reactivase proteins to restore activity (PubMed: 11557314).

Other names

Glycerol hydro-lyaseB12-dependent glycerol dehydratasePropanediol dehydratase

The enzyme utilizes a radical-mediated mechanism involving adenosylcobalamin to dehydrate glycerol; drugs like cobalamin analogs can modulate activity by competing for the cofactor binding site or through mechanism-based inactivation (PubMed: 15522861).