Functional genomic analysis of alkaloid biosynthesis in Hyoscyamus niger reveals a cytochrome P450 involved in littorine rearrangement

Chem Biol. 2006 May;13(5):513-20. doi: 10.1016/j.chembiol.2006.03.005.


Tropane alkaloids are valuable pharmaceutical drugs derived from solanaceous plants such as Hyoscyamus niger (black henbane). The biosynthesis of these molecules, including the nature of the enigmatic rearrangement of (R)-littorine to (S)-hyoscyamine, is not completely understood. To test the hypothesis that a cytochrome P450 enzyme is involved in this rearrangement, we used virus-induced gene silencing to silence a cytochrome P450, CYP80F1, identified from H. niger roots by EST sequencing. Silencing CYP80F1 resulted in reduced hyoscyamine levels and the accumulation of littorine. Hyoscyamine was observed in CYP80F1-expressing tobacco hairy roots supplied with (R)-littorine. Expression in yeast confirmed that CYP80F1 catalyzes the oxidation of (R)-littorine with rearrangement to form hyoscyamine aldehyde, a putative precursor to hyoscyamine, and without rearrangement to form 3'-hydroxylittorine. Our data strongly support the involvement of CYP80F1 in the rearrangement of littorine to hyoscyamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / biosynthesis*
  • Atropine Derivatives / metabolism*
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • DNA, Complementary
  • Expressed Sequence Tags
  • Gene Silencing
  • Genome, Plant*
  • Hyoscyamus / genetics*
  • Molecular Sequence Data
  • RNA Interference
  • Saccharomyces cerevisiae / genetics


  • Alkaloids
  • Atropine Derivatives
  • DNA, Complementary
  • littorine
  • Cytochrome P-450 Enzyme System

Associated data

  • GENBANK/DQ387048