Transprenyltransferases

Transprenyltransferases, or trans-prenyltransferases, are enzymes that catalyze the sequential head-to-tail condensation of isoprenoid units to form longer chain prenyl pyrophosphates with trans-configured double bonds. They drive the production of terpenoid lipids and other isoprenoid-derived metabolites by transferring allylic prenyl groups from donors such as dimethylallyl pyrophosphate (DMAPP) or longer allylic diphosphates to isopentenyl pyrophosphate (IPP), yielding compounds like GPP, FPP, and GGPP.

The trans-prenyltransferase family includes enzymes such as farnesyl pyrophosphate synthase (FPPS), geranylgeranyl pyrophosphate synthase (GGPPS), undecaprenyl pyrophosphate synthase (UPPS), and octaprenyl pyrophosphate synthase (OPPS). In eukaryotes, protein farnesyltransferase and geranylgeranyltransferases I and II are trans-prenyltransferases that attach a farnesyl or geranylgeranyl group to cysteine residues in CaaX motifs as a post-translational modification, which targets proteins to membranes. Trans-prenyltransferases typically rely on conserved aspartate-rich motifs, such as FARM and SARM, to coordinate magnesium ions and stabilize reaction intermediates. Elongation proceeds by successive condensations to produce polyprenyl pyrophosphates of defined lengths.

Biological roles include provisioning lipid carriers for cell wall biosynthesis in bacteria and generating substrates for downstream terpenoid pathways. They are of interest in metabolic engineering for altering terpenoid profiles in microbes and plants, and they are contrasted with cis-prenyltransferases, which produce cis-configured products and often employ different structural frameworks.