Phosphoenolpyruvate synthase (PPS)

Phosphoenolpyruvate synthase (PPS) is a critical enzyme primarily found in bacteria, archaea, and some plants, where it catalyzes the first committed step of gluconeogenesis by converting pyruvate into phosphoenolpyruvate (PEP). This reaction is unique because it utilizes the high-energy bonds of ATP to drive the phosphorylation of pyruvate, producing AMP and inorganic phosphate as byproducts through a histidyl-phosphoenzyme intermediate (UniProt P23538; PubMed 10480878). While humans utilize a different pathway involving pyruvate carboxylase and PEP carboxykinase to achieve this conversion, the presence of PPS in significant pathogens like Escherichia coli and Mycobacterium tuberculosis makes it a potential target for novel antimicrobial development (PubMed 25654531). Inhibiting this enzyme could disrupt the ability of pathogens to synthesize glucose from three-carbon precursors, which is essential for survival during certain stages of infection. Currently, there are no FDA-approved drugs targeting PPS, but it remains a subject of interest in metabolic engineering and the search for narrow-spectrum antibiotics that do not interfere with human metabolic machinery.

Other names

Phosphoenolpyruvate synthetasePyruvate, water dikinasePEP synthasePEPS

Catalyzes the conversion of pyruvate and ATP to phosphoenolpyruvate (PEP), AMP, and inorganic phosphate via a phosphorylated enzyme intermediate.