Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of Epoxides
Environmentally friendly processes are nowadays a trending topic to get highly desired chemical compounds and, in this sense, the use of enzyme-catalyzed routes is becoming a promising alternative to traditional synthetic methods. In the present paper, a hybrid quantum mechanics/molecular mechanics...
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ftunivjaumeirep:oai:repositori.uji.es:10234/194941 2023-05-15T13:58:37+02:00 Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of Epoxides Galmés, Miquel À Świderek, Katarzyna Moliner, Vicent 2021-10-08T06:56:40Z application/pdf http://hdl.handle.net/10234/194941 https://doi.org/10.1021/acs.jcim.1c00425 eng eng American Chemical Society J. Chem. Inf. Model. 2021, 61, 3604−3614 https://pubs.acs.org/doi/10.1021/acs.jcim.1c00425 https://pubs.acs.org/journal/jcisd8 Miquel A. Galmés, Katarzyna Świderek, and Vicent Moliner Journal of Chemical Information and Modeling 2021 61 (7), 3604-3614 DOI:10.1021/acs.jcim.1c00425 1549-9596 1549-960X http://hdl.handle.net/10234/194941 https://doi.org/10.1021/acs.jcim.1c00425 © 2021 American Chemical Society http://rightsstatements.org/vocab/InC/1.0/ info:eu-repo/semantics/openAccess hydrocarbons oxides peptides and proteins organic reactions chemical reactions info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/acceptedVersion 2021 ftunivjaumeirep https://doi.org/10.1021/acs.jcim.1c00425 2022-10-11T23:05:36Z Environmentally friendly processes are nowadays a trending topic to get highly desired chemical compounds and, in this sense, the use of enzyme-catalyzed routes is becoming a promising alternative to traditional synthetic methods. In the present paper, a hybrid quantum mechanics/molecular mechanics (QM/MM) computational study on the epoxidation of alkenes catalyzed by the Ser105Ala variant of the promiscuous Candida antarctica lipase B (CALB) is presented in an attempt to search for alternative paths to get useful intermediates in industries. The catalyzed reaction, described at the atomistic level with a model of the full solvated in a box of water molecules, is compared with the alternative epoxidation of alkenes by peroxy acids in chloroform. Free-energy profiles obtained at the density functional theory (DFT)/MM level show how Ser105Ala CALB is capable of epoxide short alkenes in a two-step process with free-energy barriers, in agreement with available experimental data, that are significantly lower than those of the single-step reaction in solution. The possible (R)-enantioselectivity dictated by the binding step, explored by means of alchemical QM/MM free-energy perturbation (FEP) methods, and the preference for the (S)-enantiomer derived from the free-energy landscape of the chemical steps would cancel out, thus predicting the lack of enantioselectivity experimentally observed. In general, our results provide general information on the molecular mechanism employed by a highly promiscuous enzyme, with potential applications in biotechnology. Article in Journal/Newspaper Antarc* Antarctica Repositori Universitat Jaume I (Repositorio UJI) Journal of Chemical Information and Modeling 61 7 3604 3614 |
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Repositori Universitat Jaume I (Repositorio UJI) |
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ftunivjaumeirep |
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English |
topic |
hydrocarbons oxides peptides and proteins organic reactions chemical reactions |
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hydrocarbons oxides peptides and proteins organic reactions chemical reactions Galmés, Miquel À Świderek, Katarzyna Moliner, Vicent Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of Epoxides |
topic_facet |
hydrocarbons oxides peptides and proteins organic reactions chemical reactions |
description |
Environmentally friendly processes are nowadays a trending topic to get highly desired chemical compounds and, in this sense, the use of enzyme-catalyzed routes is becoming a promising alternative to traditional synthetic methods. In the present paper, a hybrid quantum mechanics/molecular mechanics (QM/MM) computational study on the epoxidation of alkenes catalyzed by the Ser105Ala variant of the promiscuous Candida antarctica lipase B (CALB) is presented in an attempt to search for alternative paths to get useful intermediates in industries. The catalyzed reaction, described at the atomistic level with a model of the full solvated in a box of water molecules, is compared with the alternative epoxidation of alkenes by peroxy acids in chloroform. Free-energy profiles obtained at the density functional theory (DFT)/MM level show how Ser105Ala CALB is capable of epoxide short alkenes in a two-step process with free-energy barriers, in agreement with available experimental data, that are significantly lower than those of the single-step reaction in solution. The possible (R)-enantioselectivity dictated by the binding step, explored by means of alchemical QM/MM free-energy perturbation (FEP) methods, and the preference for the (S)-enantiomer derived from the free-energy landscape of the chemical steps would cancel out, thus predicting the lack of enantioselectivity experimentally observed. In general, our results provide general information on the molecular mechanism employed by a highly promiscuous enzyme, with potential applications in biotechnology. |
format |
Article in Journal/Newspaper |
author |
Galmés, Miquel À Świderek, Katarzyna Moliner, Vicent |
author_facet |
Galmés, Miquel À Świderek, Katarzyna Moliner, Vicent |
author_sort |
Galmés, Miquel À |
title |
Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of Epoxides |
title_short |
Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of Epoxides |
title_full |
Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of Epoxides |
title_fullStr |
Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of Epoxides |
title_full_unstemmed |
Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of Epoxides |
title_sort |
computational studies suggest promiscuous candida antarctica lipase b as an environmentally friendly alternative for the production of epoxides |
publisher |
American Chemical Society |
publishDate |
2021 |
url |
http://hdl.handle.net/10234/194941 https://doi.org/10.1021/acs.jcim.1c00425 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
J. Chem. Inf. Model. 2021, 61, 3604−3614 https://pubs.acs.org/doi/10.1021/acs.jcim.1c00425 https://pubs.acs.org/journal/jcisd8 Miquel A. Galmés, Katarzyna Świderek, and Vicent Moliner Journal of Chemical Information and Modeling 2021 61 (7), 3604-3614 DOI:10.1021/acs.jcim.1c00425 1549-9596 1549-960X http://hdl.handle.net/10234/194941 https://doi.org/10.1021/acs.jcim.1c00425 |
op_rights |
© 2021 American Chemical Society http://rightsstatements.org/vocab/InC/1.0/ info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1021/acs.jcim.1c00425 |
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Journal of Chemical Information and Modeling |
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61 |
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7 |
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3604 |
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3614 |
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1766266975774834688 |