Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase

Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14777-82. doi: 10.1073/pnas.96.26.14777.


Pyrrolizidine alkaloids are preformed plant defense compounds with sporadic phylogenetic distribution. They are thought to have evolved in response to the selective pressure of herbivory. The first pathway-specific intermediate of these alkaloids is the rare polyamine homospermidine, which is synthesized by homospermidine synthase (HSS). The HSS gene from Senecio vernalis was cloned and shown to be derived from the deoxyhypusine synthase (DHS) gene, which is highly conserved among all eukaryotes and archaebacteria. DHS catalyzes the first step in the activation of translation initiation factor 5A (eIF5A), which is essential for eukaryotic cell proliferation and which acts as a cofactor of the HIV-1 Rev regulatory protein. Sequence comparison provides direct evidence for the evolutionary recruitment of an essential gene of primary metabolism (DHS) for the origin of the committing step (HSS) in the biosynthesis of pyrrolizidine alkaloids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / genetics*
  • Alkyl and Aryl Transferases / metabolism
  • Amino Acid Sequence
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Evolution, Molecular*
  • Magnoliopsida / chemistry
  • Molecular Sequence Data
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Oxidoreductases Acting on CH-NH Group Donors / metabolism
  • Plant Roots / enzymology
  • Plants, Toxic*
  • Polymerase Chain Reaction
  • Pyrrolizidine Alkaloids / metabolism*
  • Recombinant Proteins / metabolism
  • Senecio / enzymology
  • Senecio / genetics*
  • Sequence Analysis, DNA
  • Sequence Analysis, Protein
  • Sequence Homology, Amino Acid


  • DNA, Complementary
  • Pyrrolizidine Alkaloids
  • Recombinant Proteins
  • Oxidoreductases Acting on CH-NH Group Donors
  • deoxyhypusine synthase
  • Alkyl and Aryl Transferases
  • homospermidine synthetase

Associated data

  • GENBANK/AJ238622
  • GENBANK/AJ238623
  • GENBANK/AJ238624