CPT

PF3D7_0826400 (CPT) is an active cis-prenyltransferase of Plasmodium falciparum that catalyzes de novo polyprenyl chain elongation, producing polyprenols of 15–19 isoprene units as the committed step of the parasite's dolichol biosynthesis pathway; the polyprenol product is subsequently reduced to dolichol by the polyprenol reductase PfPPRD (PMID:32764679). Its cis-polyisoprenoid output yields a polyprenol and dolichol profile that varies across the intraerythrocytic asexual cycle and differs between asexual and gametocyte stages, indicating stage-specific regulation of the enzyme (PMID:32764679). Phylogenetic analysis predicts CPT is the catalytic subunit of a heteromeric enzyme that would require an as-yet-unidentified accessory subunit, but no such partner has been experimentally identified in Plasmodium (PMID:40847593). Beyond these findings, the enzyme has not been reconstituted in vitro, mutagenized, or structurally characterized in the available corpus.

1. 2020 Medium

   Whether Plasmodium falciparum encodes a functional cis-prenyltransferase feeding dolichol biosynthesis was resolved by confirming CPT catalyzes polyprenol chain elongation in the parasite.

   Evidence Metabolomics profiling plus confirmation of enzymatic activity in intraerythrocytic and gametocyte stages

   PMID:32764679

   Open questions at the time

   • No in vitro reconstitution or mutagenesis of the purified protein
   • Chain-length specificity determinants not dissected
   • Subcellular localization of the enzyme not established
2. 2020 Low

   To ask whether CPT output is developmentally controlled, polyprenol/dolichol profiles were tracked across stages, revealing stage-specific differences that imply regulated CPT activity.

   Evidence Metabolomics profiling across intraerythrocytic asexual and gametocyte developmental stages

   PMID:32764679

   Open questions at the time

   • Single lab, single metabolomics method with no direct mechanistic dissection of CPT regulation
   • Transcriptional versus post-translational control of activity unresolved
   • Whether profile changes reflect CPT abundance or activity is unknown
3. 2025 Low

   To address the enzyme's quaternary organization, phylogenetic analysis predicted CPT is a catalytic subunit requiring an accessory subunit for a fully active heteromeric complex.

   Evidence Comparative/phylogenetic analysis; no direct Plasmodium experiment performed

   PMID:40847593

   Open questions at the time

   • Computational prediction only, with no experimental validation in Plasmodium
   • No CPT accessory subunit partner identified in Plasmodium
   • Complex stoichiometry and requirement for activity untested

• Whether CPT functions as a heteromeric enzyme in Plasmodium and the identity of any accessory subunit remain unknown.
• No experimentally identified CPT accessory subunit
• No structural or reconstitution data for the putative complex