Enzymatic cyclization of 22,23-dihydro-2,3-oxidosqualene into euph-7-en-3beta-ol and bacchar-12-en-3beta-ol by recombinant beta-amyrin synthase

J Am Chem Soc. 2004 Mar 24;126(11):3426-7. doi: 10.1021/ja031955v.

Abstract

Recombinant beta-amyrin synthase from Pisum sativum converted 22,23-dihydro-2,3-oxidosqualene, a substrate analogue lacking the terminal double bond of 2,3-oxidosqualene, into a 4:1 mixture of euph-7-en-3beta-ol and bacchar-12-en-3beta-ol. This is the first demonstration of the enzymatic formation of the baccharene skeleton with a six-membered D-ring. In the absence of the terminal double bond, the proton-initiated cyclization first generated the tetracyclic dammarenyl cation, followed by a backbone rearrangement with loss of H-7alpha leading to the formation of euph-7-en-3beta-ol, while D-ring expansion to the baccharenyl cation and subsequent 1,2-hydride shifts with H-12alpha elimination yielded bacchar-12-en-3beta-ol. It is remarkable that the formation of the anti-Markovnikov six-membered D-ring did not depend on the participation of the terminal pi-electrons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclization
  • Intramolecular Transferases / chemistry*
  • Intramolecular Transferases / metabolism
  • Lanosterol / analogs & derivatives*
  • Lanosterol / chemical synthesis*
  • Lanosterol / metabolism
  • Pisum sativum / enzymology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Squalene / analogs & derivatives*
  • Squalene / chemical synthesis*
  • Squalene / metabolism
  • Triterpenes / chemical synthesis*
  • Triterpenes / metabolism

Substances

  • 2,3-oxidosqualene
  • Recombinant Proteins
  • Triterpenes
  • bacchar-12-en-3beta-ol
  • Lanosterol
  • euphol
  • Squalene
  • Intramolecular Transferases
  • 2,3-oxidosqualene-beta-amyrin-cyclase