HMBPP

HMBPP stands for 4-hydroxy-3-methylbut-2-enyl pyrophosphate. It is a phosphorylated allylic metabolite in the non-mevalonate (MEP/DOXP) pathway of isoprenoid biosynthesis. This pathway operates in many bacteria, plant plastids, and some algae and protozoa, and it provides the universal isoprenoid precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). Humans rely on the mevalonate pathway instead, making the MEP pathway a notable target for antimicrobial research.

Biochemistry and role: In the MEP pathway, HMBPP is formed near the end from methylerythritol phosphate through the actions of IspG and IspH. HMBPP then serves as the direct substrate for the last step, being reduced by the enzyme HMBPP reductase (encoded by lytB) to IPP and DMAPP, which are subsequently used to synthesize a wide range of isoprenoids, including quinones, carotenoids, and cell wall precursors.

Distribution and significance: HMBPP is a key intermediate in organisms that utilize the MEP pathway. Because humans do not possess this pathway, targeting enzymes that generate or convert HMBPP (such as IspG, IspH, or HMBPP reductase) is of interest for developing antibiotics or antiparasitic agents.

Research and applications: Beyond metabolism, HMBPP and its pathway enzymes are studied in structural biology and drug discovery to understand reaction mechanisms and to screen for inhibitors that disrupt isoprenoid biosynthesis in pathogens.