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Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline
Reductive aminases (RedAms) for the stereoselective amination of ketones represent an environmentally benign and economically viable alternative to transition metal–catalyzed asymmetric chemical synthesis. Here, we report two RedAms from Aspergillus calidoustus (AcRedAm) and bacteria (BaRedAm) with...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727753/ https://www.ncbi.nlm.nih.gov/pubmed/35004654 http://dx.doi.org/10.3389/fbioe.2021.798147 |
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author | Zhang, Kai He, Yuanzhi Zhu, Jiawei Zhang, Qi Tang, Luyao Cui, Li Feng, Yan |
author_facet | Zhang, Kai He, Yuanzhi Zhu, Jiawei Zhang, Qi Tang, Luyao Cui, Li Feng, Yan |
author_sort | Zhang, Kai |
collection | PubMed |
description | Reductive aminases (RedAms) for the stereoselective amination of ketones represent an environmentally benign and economically viable alternative to transition metal–catalyzed asymmetric chemical synthesis. Here, we report two RedAms from Aspergillus calidoustus (AcRedAm) and bacteria (BaRedAm) with NADPH-dependent features. The enzymes can synthesize a set of secondary amines using a broad range of ketone and amine substrates with up to 97% conversion. To synthesize the pharmaceutical ingredient (R)-rasagiline, we engineered AcRedAm through rational design to obtain highly stereoselective mutants. The best mutant Q237A from AcRedAm could synthesize (R)-rasagiline with >99% enantiomeric excess with moderate conversion. The features of AcRedAm and BaRedAm highlight their potential for further study and expand the biocatalytic toolbox for industrial applications. |
format | Online Article Text |
id | pubmed-8727753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87277532022-01-06 Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline Zhang, Kai He, Yuanzhi Zhu, Jiawei Zhang, Qi Tang, Luyao Cui, Li Feng, Yan Front Bioeng Biotechnol Bioengineering and Biotechnology Reductive aminases (RedAms) for the stereoselective amination of ketones represent an environmentally benign and economically viable alternative to transition metal–catalyzed asymmetric chemical synthesis. Here, we report two RedAms from Aspergillus calidoustus (AcRedAm) and bacteria (BaRedAm) with NADPH-dependent features. The enzymes can synthesize a set of secondary amines using a broad range of ketone and amine substrates with up to 97% conversion. To synthesize the pharmaceutical ingredient (R)-rasagiline, we engineered AcRedAm through rational design to obtain highly stereoselective mutants. The best mutant Q237A from AcRedAm could synthesize (R)-rasagiline with >99% enantiomeric excess with moderate conversion. The features of AcRedAm and BaRedAm highlight their potential for further study and expand the biocatalytic toolbox for industrial applications. Frontiers Media S.A. 2021-12-22 /pmc/articles/PMC8727753/ /pubmed/35004654 http://dx.doi.org/10.3389/fbioe.2021.798147 Text en Copyright © 2021 Zhang, He, Zhu, Zhang, Tang, Cui and Feng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Zhang, Kai He, Yuanzhi Zhu, Jiawei Zhang, Qi Tang, Luyao Cui, Li Feng, Yan Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline |
title | Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline |
title_full | Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline |
title_fullStr | Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline |
title_full_unstemmed | Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline |
title_short | Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline |
title_sort | engineering of reductive aminases for asymmetric synthesis of enantiopure rasagiline |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727753/ https://www.ncbi.nlm.nih.gov/pubmed/35004654 http://dx.doi.org/10.3389/fbioe.2021.798147 |
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