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.
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.
Abe
Ikuro
I
School of Pharmaceutical Sciences and the COE 21 Program, University of Shizuoka, Shizuoka 422-8526, Japan.
Sakano
Yuichi
Y
Tanaka
Hideya
H
Lou
Weiwei
W
Noguchi
Hiroshi
H
Shibuya
Masaaki
M
Ebizuka
Yutaka
Y
D003500:Cyclization; D019751:Intramolecular Transferases / Q000737:chemistry* / Q000378:metabolism; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism; D018532:Pisum sativum / Q000201:enzymology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013185:Squalene / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism; D014315:Triterpenes / Q000138:chemical synthesis* / Q000378:metabolism
C002821:2,3-oxidosqualene; D011994:Recombinant Proteins; D014315:Triterpenes; C486107:bacchar-12-en-3beta-ol; D007810:Lanosterol; C062557:euphol; D013185:Squalene; D019751:Intramolecular Transferases; C039924:2,3-oxidosqualene-beta-amyrin-cyclase