3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBP synthase (also commonly RibB))

3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBP synthase, also known as RibB) is a magnesium-dependent enzyme (EC 4.1.99.12) required for the riboflavin (vitamin B2) biosynthesis pathway in bacteria, plants, and fungi, but is absent in humans. It catalyzes the conversion of D-ribulose 5-phosphate into 3,4-dihydroxy-2-butanone 4-phosphate (a direct precursor of the riboflavin isoalloxazine/xylene ring) and formate. The reaction represents a committed step of the riboflavin pathway, making the enzyme indispensable for the survival of many bacterial pathogens, including Mycobacterium tuberculosis, Salmonella, and Helicobacter species, in which the ribB gene is essential. Its absence in humans, together with its essentiality in bacterial pathogens, has led to its consideration as a promising antibacterial drug target. Various biochemical and structural studies have elucidated the catalytic mechanism and identified candidate inhibitors such as 4PEH that act via competitive inhibition, although no drugs targeting DHBP synthase have reached clinical development. In some organisms, the enzyme may exist as part of a bifunctional protein with GTP cyclohydrolase II, participating in early steps of riboflavin biosynthesis. DHBP synthase is classified as an enzyme and is currently not recognized as a clinical biomarker nor are notable safety concerns reported for its inhibition due to its absence in human metabolism.

Other names

DHBP synthaseRibBL-3,4-dihydroxybutan-2-one-4-phosphate synthase

Competitive inhibition of substrate binding (as demonstrated by 4PEH); (Potential) small molecule inhibition disrupting riboflavin biosynthesis pathway