Print Email Facebook Twitter Asymmetric Cation-Olefin Monocyclization by Engineered Squalene–Hopene Cyclases Title Asymmetric Cation-Olefin Monocyclization by Engineered Squalene–Hopene Cyclases Author Eichenberger, Michael (Zurich University of Applied Science (ZHAW)) Hüppi, S.N. (TU Delft BT/Biocatalysis; Zurich University of Applied Science (ZHAW)) Patsch, David (Zurich University of Applied Science (ZHAW); Greifswald University) Aeberli, Natalie (Fragrances S & T, Kemptthal) Berweger, Raphael (Fragrances S & T, Kemptthal) Dossenbach, Sandro (Fragrances S & T, Kemptthal) Eichhorn, Eric (Fragrances S & T, Kemptthal) Flachsmann, Felix (Fragrances S & T, Kemptthal) Hortencio, Lucas (Fragrances S & T, Kemptthal) Date 2021 Abstract Squalene–hopene cyclases (SHCs) have great potential for the industrial synthesis of enantiopure cyclic terpenoids. A limitation of SHC catalysis has been the enzymes’ strict (S)-enantioselectivity at the stereocenter formed after the first cyclization step. To gain enantio-complementary access to valuable monocyclic terpenoids, an SHC-wild-type library including 18 novel homologs was set up. A previously not described SHC (AciSHC) was found to synthesize small amounts of monocyclic (R)-γ-dihydroionone from (E/Z)-geranylacetone. Using enzyme and process optimization, the conversion to the desired product was increased to 79 %. Notably, analyzed AciSHC variants could finely differentiate between the geometric geranylacetone isomers: While the (Z)-isomer yielded the desired monocyclic (R)-γ-dihydroionone (>99 % ee), the (E)-isomer was converted to the (S,S)-bicyclic ether (>95 % ee). Applying the knowledge gained from the observed stereodivergent and enantioselective transformations to an additional SHC-substrate pair, access to the complementary (S)-γ-dihydroionone (>99.9 % ee) could be obtained. Subject chemoenzymatic synthesiscyclizationprotein engineeringsqualene–hopene cyclasessubstrate engineering To reference this document use: http://resolver.tudelft.nl/uuid:086bf9f2-595c-4a77-8a62-f2f228b67581 DOI https://doi.org/10.1002/anie.202108037 ISSN 1433-7851 Source Angewandte Chemie (International Edition), 60 (50), 26080-26086 Part of collection Institutional Repository Document type journal article Rights © 2021 Michael Eichenberger, S.N. Hüppi, David Patsch, Natalie Aeberli, Raphael Berweger, Sandro Dossenbach, Eric Eichhorn, Felix Flachsmann, Lucas Hortencio, More Authors Files PDF Angewandte_Chemie_Intl_Ed ... Hopene.pdf 1.58 MB Close viewer /islandora/object/uuid:086bf9f2-595c-4a77-8a62-f2f228b67581/datastream/OBJ/view