prenyltransferases

Prenyltransferases are enzymes that catalyze the transfer of prenyl groups from prenyl diphosphates to acceptor molecules, forming carbon–carbon bonds in isoprenoid biosynthesis. They are generally divided into cis-prenyltransferases, which assemble long-chain polyprenols via cis additions, and trans-prenyltransferases, which perform head-to-tail additions to yield shorter to medium-length polyprenyl chains such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate. The products serve as essential precursors for terpenoids, quinones, and lipids, or act as lipid carriers in cell wall biosynthesis.

Trans-prenyltransferases include enzymes that condense isoprenoid units to form allylic diphosphates: examples include geranylgeranyl pyrophosphate synthase and farnesyl pyrophosphate synthase. They often function as homodimers or heterodimeric complexes and require divalent metal ions. Conserved motifs such as aspartate-rich regions coordinate metal ions and allylic substrates. In eukaryotes, specific trans-prenyltransferases attach FPP or GGPP to cysteine residues on protein substrates in a process called protein prenylation, performed by farnesyltransferase, geranylgeranyl transferase I, and Rab geranylgeranyl transferase. Prenylation promotes membrane association and function of signaling proteins such as Ras and Rab family GTPases. Aberrant prenylation is implicated in disease; inhibitors of FTase have been investigated in cancer therapy, and bacterial trans-prenyltransferases are drug targets for antibiotics.

Cis-prenyltransferases synthesize long-chain polyprenyl chains used to generate lipid carriers such as undecaprenyl phosphate in bacteria and dolichol in eukaryotes. These carriers donate prenyl lipids for glycan assembly and protein glycosylation processes across membranes. Cis-prenyltransferases are generally membrane-associated and produce very long chains through repeated cis additions.

Evolutionarily diverse, prenyltransferases are found across bacteria, archaea, and eukaryotes, reflecting the central role of isoprenoids in cellular metabolism.