Prenyltransferase

Prenyltransferases are a diverse family of enzymes that catalyze the transfer of prenyl groups, isoprenoid units, from prenyl diphosphate donors to various acceptor molecules. Their activity links the biosynthesis of terpenoids and related lipids to primary and secondary metabolism in all domains of life. The common donors are allylic pyrophosphates such as dimethylallyl pyrophosphate (DMAPP), geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), and extending units like isopentenyl pyrophosphate (IPP). The reactions typically produce longer-chain prenyl pyrophosphates and release inorganic pyrophosphate.

A major subdivision is the normal or trans-prenyltransferases, which perform sequential condensations to elongate the isoprenoid chain in a head-to-tail fashion. Examples include geranyl pyrophosphate synthase, farnesyl pyrophosphate synthase, and geranylgeranyl pyrophosphate synthase. These enzymes generate key intermediates such as GPP, FPP, and GGPP that feed into the synthesis of sterols, ubiquinones, carotenoids, and other terpenoids.

In addition to metabolic polyprenyltransferases, there are protein prenyltransferases that modify proteins post-translationally. Farnesyltransferase and geranylgeranyltransferases I and II catalyze the attachment of farnesyl or geranylgeranyl groups to cysteine residues within CaaX or related motifs, enabling membrane association and proper protein localization. Rab geranylgeranyltransferase specifically modifies Rab GTPases and influences vesicular trafficking.

Overall, prenyltransferases play essential roles in cell biology, membrane integrity, and the production of diverse natural products, with some members serving as targets for therapeutic intervention.