Asymmetric Cation-Olefin Monocyclization by Engineered Squalene-Hopene Cyclases.

Autor: Eichenberger M; Zurich University of Applied Sciences, Life Sciences and Facility Management, Einsiedlerstrasse 31, 8820, Wädenswil, Switzerland., Hüppi S; Zurich University of Applied Sciences, Life Sciences and Facility Management, Einsiedlerstrasse 31, 8820, Wädenswil, Switzerland.; Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629, HZ, Delft, The Netherlands., Patsch D; Zurich University of Applied Sciences, Life Sciences and Facility Management, Einsiedlerstrasse 31, 8820, Wädenswil, Switzerland.; Institute of Biochemistry, Dept. of Biotechnology & Enzyme Catalysis, Greifswald University, Felix-Hausdorff-Strasse 4, 17487, Greifswald, Germany., Aeberli N; Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptpark 50, 8310, Kemptthal, Switzerland., Berweger R; Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptpark 50, 8310, Kemptthal, Switzerland., Dossenbach S; Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptpark 50, 8310, Kemptthal, Switzerland., Eichhorn E; Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptpark 50, 8310, Kemptthal, Switzerland., Flachsmann F; Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptpark 50, 8310, Kemptthal, Switzerland., Hortencio L; Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptpark 50, 8310, Kemptthal, Switzerland., Voirol F; Fragrances S&T, Ingredients Research, Givaudan Schweiz AG, Kemptpark 50, 8310, Kemptthal, Switzerland., Vollenweider S; Science & Technology, Givaudan International SA, Kemptpark 50, 8310, Kemptthal, Switzerland., Bornscheuer UT; Institute of Biochemistry, Dept. of Biotechnology & Enzyme Catalysis, Greifswald University, Felix-Hausdorff-Strasse 4, 17487, Greifswald, Germany., Buller R; Zurich University of Applied Sciences, Life Sciences and Facility Management, Einsiedlerstrasse 31, 8820, Wädenswil, Switzerland.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Dec 06; Vol. 60 (50), pp. 26080-26086. Date of Electronic Publication: 2021 Sep 17.
DOI: 10.1002/anie.202108037
Abstrakt: 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.
(© 2021 The Authors. Published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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