Asymmetric Cation‐Olefin Monocyclization by Engineered Squalene–Hopene Cyclases

Squalene–hopene cyclases (SHCs) have great potential for the industrial synthesis of enantiopure cyclic terpenoids. A limitation SHC catalysis has been enzymes’ strict (S)-enantioselectivity at stereocenter formed after first cyclization step. To gain enantio-complementary access to valuable monocyclic terpenoids, an SHC-wild-type library including 18 novel homologs was set up. previously not described (AciSHC) found synthesize small amounts (R)-γ-dihydroionone from (E/Z)-geranylacetone. Using enzyme and process optimization, conversion desired product increased 79 %. Notably, analyzed AciSHC variants could finely differentiate between geometric geranylacetone isomers: While (Z)-isomer yielded (>99 % ee), (E)-isomer converted (S,S)-bicyclic ether (>95 ee). Applying knowledge gained observed stereodivergent enantioselective transformations additional SHC-substrate pair, complementary (S)-γ-dihydroionone (>99.9 ee) be obtained.