A recent report describes the cloning and preliminary characterization of an unusual flavin mononucleotide (FMN) dependent enzyme, the type II isopentenyl diphosphate (IPP) isomerase. IPP isomerases interconvert isopentenyl diphosphate and dimethylallyl diphosphate, the metabolic building blocks for a wide array of biological isoprenoid compounds. The newly identified type II enzyme represents an attractive antimicrobial drug target as sequence analyses suggest that it is essential in the pathogen Staphylococcus aureus and is not present in humans. The initial study with the type II IPP isomerase indicated that catalysis requires both FMN and NADPH. The role is these two cofactors is unclear, given that isomerization does not entail a net oxidation/reduction and that the type l isomerase catalyzes a proton addition-proton elimination reaction that does not include a transient oxidation/reduction. This proposed work intends to elucidate the functions of the two cofactors, the chemical mechanism, and the roles of active site residues in the reaction catalyzed by type II isopentenyl diphosphate isomerase from Synechocystis sp. PCC 6803.
