A solanesyl-diphosphate synthase localizes in glycosomes of Trypanosoma cruzi

J Biol Chem. 2006 Dec 22;281(51):39339-48. doi: 10.1074/jbc.M607451200. Epub 2006 Oct 24.


We report the cloning of a Trypanosoma cruzi gene encoding a solanesyl-diphosphate synthase, TcSPPS. The amino acid sequence (molecular mass approximately 39 kDa) is homologous to polyprenyl-diphosphate synthases from different organisms, showing the seven conserved motifs and the typical hydrophobic profile. TcSPPS preferred geranylgeranyl diphosphate as the allylic substrate. The final product, as determined by TLC, had nine isoprene units. This suggests that the parasite synthesizes mainly ubiquinone-9 (UQ-9), as described for Trypanosoma brucei and Leishmania major. In fact, that was the length of the ubiquinone extracted from epimastigotes, as determined by high-performance liquid chromatography. Expression of TcSPPS was able to complement an Escherichia coli ispB mutant. A punctuated pattern in the cytoplasm of the parasite was detected by immunofluorescence analysis with a specific polyclonal antibody against TcSPPS. An overlapping fluorescence pattern was observed using an antibody directed against the glycosomal marker pyruvate phosphate dikinase, suggesting that this step of the isoprenoid biosynthetic pathway is located in the glycosomes. Co-localization in glycosomes was confirmed by immunogold electron microscopy and subcellular fractionation. Because UQ has a central role in energy production and in reoxidation of reduction equivalents, TcSPPS is promising as a new chemotherapeutic target.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / biosynthesis*
  • Alkyl and Aryl Transferases / chemistry
  • Amino Acid Sequence
  • Animals
  • Chromatography, Thin Layer
  • Cloning, Molecular
  • Cosmids
  • Escherichia coli / metabolism
  • Genetic Complementation Test
  • Microbodies / metabolism*
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Trypanosoma cruzi / metabolism*
  • Ubiquinone / chemistry
  • Ubiquinone / isolation & purification


  • Ubiquinone
  • Alkyl and Aryl Transferases
  • trans-octaprenyltranstransferase
  • ubiquinone 9

Associated data

  • GENBANK/AF282771