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Selectivity in the Cyclization of Citronellal Introduced by Squalene Hopene Cyclase Variants
Author(s) -
Bastian Silke A.,
Hammer Stephan C.,
Kreß Nico,
Nestl Bettina M.,
Hauer Bernhard
Publication year - 2017
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201700734
Subject(s) - citronellal , chemistry , catalysis , stereoselectivity , selectivity , squalene , cyclase , stereochemistry , organic chemistry , enzyme
Abstract The squalene hopene cyclase from Alicyclobacillus acidocaldarius ( Aac SHC) is a highly efficient enzyme catalyst for stereoselective Brønsted acid catalysis. We engineered Aac SHC to catalyze the selective Prins cyclization of citronellal. Four active site variants were identified for the diastereoselective cyclization of ( S )‐citronellal to stereoisomers (−)‐ iso ‐isopulegol, (+)‐isopulegol and (−)‐ neo ‐isopulegol, respectively. The replacement of active site residues resulted in two triple variants that catalyzed the transformation of ( R )‐citronellal to give the isomers (+)‐ neo ‐isopulegol and (−)‐isopulegol with up to >99 % de , respectively. The newly designed library of functionally diverse active site geometries exhibits high selective control during citronellal cyclization, leading exclusively to a single diastereomer of the desired isopulegol. Whereas the cyclization of citronellal with chemical catalysts was observed to produce the isopulegol isomer with the lowest energy, the reaction with Aac SHC variants proceeded with higher product selectivity. The results of this study show that variants of Aac SHC are excellent catalysts for the highly selective formation of isopulegol stereoisomers.