Phosphoenolpyruvate mutase (PEP mutase)

Phosphoenolpyruvate mutase is an enzyme that catalyzes the conversion of phosphoenolpyruvate (PEP) to phosphonopyruvate, representing the first committed step in the biosynthetic pathway for phosphonates, a group of natural products that include important antibiotic molecules such as fosfomycin[1][2][3][7]. The enzyme operates by a dissociative mechanism facilitated by a magnesium cofactor and stabilizing interactions within its active site, particularly involving residues such as Asp58, Asp85, Asp87, Glu114, and Arg159[1][2][3][5]. Structurally, PEP mutase forms a modified alpha/beta-barrel fold and typically assembles into a tetramer[3][5]. It is essential in microorganisms that synthesize phosphonate-containing secondary metabolites, but is not considered a direct therapeutic target in humans[7]. The enzyme is of pharmacological and biotechnological interest due to its role in the production of bioactive phosphonates and because the formation of a stable C–P bond is a rare and chemically challenging biochemical transformation[1][3][6][9].

Other names

Phosphoenolpyruvate phosphomutasePEP mutase

Formation of C–P bond by catalyzing the conversion of phosphoenolpyruvate to phosphonopyruvate[1][2][3]. Inhibitors include oxalate and oxalyl phosphate (competitive inhibitors, used mainly as mechanistic probes rather than drugs)[4].