Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of Epoxides
comunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7013
comunitat-uji-handle3:10234/8638
comunitat-uji-handle4:
INVESTIGACIONMetadata
Title
Computational Studies Suggest Promiscuous Candida antarctica Lipase B as an Environmentally Friendly Alternative for the Production of EpoxidesDate
2021-07-26Publisher
American Chemical SocietyISSN
1549-9596; 1549-960XBibliographic citation
Miquel A. Galmés, Katarzyna Świderek, and Vicent Moliner Journal of Chemical Information and Modeling 2021 61 (7), 3604-3614 DOI: 10.1021/acs.jcim.1c00425Type
info:eu-repo/semantics/articlePublisher version
https://pubs.acs.org/journal/jcisd8Version
info:eu-repo/semantics/acceptedVersionSubject
Abstract
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 ... [+]
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. [-]
Is part of
J. Chem. Inf. Model. 2021, 61, 3604−3614Related data
https://pubs.acs.org/doi/10.1021/acs.jcim.1c00425Funder Name
Ministerio de Ciencia e Innovación | Generalitat Valenciana | Universitat Jaume I
Project code
PGC2018-094852-B-C21 | PID2019-107098RJ-I00 | AICO/2019/195 | SEJI/2020/007 | UJI-B2017-31 | UJI-A2019-04 | PREDOC/2017/23
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© 2021 American Chemical Society
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info:eu-repo/semantics/openAccess
http://rightsstatements.org/vocab/InC/1.0/
info:eu-repo/semantics/openAccess
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