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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 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 v...

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Autores principales: Eichenberger, Michael, Hüppi, Sean, Patsch, David, Aeberli, Natalie, Berweger, Raphael, Dossenbach, Sandro, Eichhorn, Eric, Flachsmann, Felix, Hortencio, Lucas, Voirol, Francis, Vollenweider, Sabine, Bornscheuer, Uwe T., Buller, Rebecca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290348/
https://www.ncbi.nlm.nih.gov/pubmed/34346556
http://dx.doi.org/10.1002/anie.202108037
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author Eichenberger, Michael
Hüppi, Sean
Patsch, David
Aeberli, Natalie
Berweger, Raphael
Dossenbach, Sandro
Eichhorn, Eric
Flachsmann, Felix
Hortencio, Lucas
Voirol, Francis
Vollenweider, Sabine
Bornscheuer, Uwe T.
Buller, Rebecca
author_facet Eichenberger, Michael
Hüppi, Sean
Patsch, David
Aeberli, Natalie
Berweger, Raphael
Dossenbach, Sandro
Eichhorn, Eric
Flachsmann, Felix
Hortencio, Lucas
Voirol, Francis
Vollenweider, Sabine
Bornscheuer, Uwe T.
Buller, Rebecca
author_sort Eichenberger, Michael
collection PubMed
description 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.
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spelling pubmed-92903482022-07-20 Asymmetric Cation‐Olefin Monocyclization by Engineered Squalene–Hopene Cyclases Eichenberger, Michael Hüppi, Sean Patsch, David Aeberli, Natalie Berweger, Raphael Dossenbach, Sandro Eichhorn, Eric Flachsmann, Felix Hortencio, Lucas Voirol, Francis Vollenweider, Sabine Bornscheuer, Uwe T. Buller, Rebecca Angew Chem Int Ed Engl Research Articles 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. John Wiley and Sons Inc. 2021-09-17 2021-12-06 /pmc/articles/PMC9290348/ /pubmed/34346556 http://dx.doi.org/10.1002/anie.202108037 Text en © 2021 The Authors. Published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Eichenberger, Michael
Hüppi, Sean
Patsch, David
Aeberli, Natalie
Berweger, Raphael
Dossenbach, Sandro
Eichhorn, Eric
Flachsmann, Felix
Hortencio, Lucas
Voirol, Francis
Vollenweider, Sabine
Bornscheuer, Uwe T.
Buller, Rebecca
Asymmetric Cation‐Olefin Monocyclization by Engineered Squalene–Hopene Cyclases
title Asymmetric Cation‐Olefin Monocyclization by Engineered Squalene–Hopene Cyclases
title_full Asymmetric Cation‐Olefin Monocyclization by Engineered Squalene–Hopene Cyclases
title_fullStr Asymmetric Cation‐Olefin Monocyclization by Engineered Squalene–Hopene Cyclases
title_full_unstemmed Asymmetric Cation‐Olefin Monocyclization by Engineered Squalene–Hopene Cyclases
title_short Asymmetric Cation‐Olefin Monocyclization by Engineered Squalene–Hopene Cyclases
title_sort asymmetric cation‐olefin monocyclization by engineered squalene–hopene cyclases
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290348/
https://www.ncbi.nlm.nih.gov/pubmed/34346556
http://dx.doi.org/10.1002/anie.202108037
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