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Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids

ABSTRACT: The introduction of β-hydroxy-α-amino acids (βHAAs) into organic molecules has received considerable attention as these molecules have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of asymmetric synthesis of βHA...

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Autores principales: Wang, Shan, Deng, Hai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072733/
https://www.ncbi.nlm.nih.gov/pubmed/33900425
http://dx.doi.org/10.1007/s00253-021-11288-w
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author Wang, Shan
Deng, Hai
author_facet Wang, Shan
Deng, Hai
author_sort Wang, Shan
collection PubMed
description ABSTRACT: The introduction of β-hydroxy-α-amino acids (βHAAs) into organic molecules has received considerable attention as these molecules have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of asymmetric synthesis of βHAAs, stereoselective synthesis to control the two chiral centres at C(α) and C(β) positions is still challenging, with poor atomic economy and multi protection and deprotection steps. These syntheses are often operated under harsh conditions. Therefore, a biotransformation approach using biocatalysts is needed to selectively introduce these two chiral centres into structurally diverse molecules. Yet, there are few ways that enable one-step synthesis of βHAAs. One is to extend the substrate scope of the existing enzyme inventory. Threonine aldolases have been explored to produce βHAAs. However, the enzymes have poor controlled installation at C(β) position, often resulting in a mixture of diastereoisomers which are difficult to be separated. In this respect, l-threonine transaldolases (LTTAs) offer an excellent potential as the enzymes often provide controlled stereochemistry at C(α) and C(β) positions. Another is to mine LTTA homologues and engineer the enzymes using directed evolution with the aim of finding engineered biocatalysts to accept broad substrates with enhanced conversion and stereoselectivity. Here, we review the development of LTTAs that incorporate various aldehyde acceptors to generate structurally diverse βHAAs and highlight areas for future developments. KEY POINTS: • The general mechanism of the transaldolation reaction catalysed by LTTAs • Recent advances in LTTAs from different biosynthetic pathways • Applications of LTTAs as biocatalysts for production of βHAAs
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spelling pubmed-80727332021-04-26 Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids Wang, Shan Deng, Hai Appl Microbiol Biotechnol Mini-Review ABSTRACT: The introduction of β-hydroxy-α-amino acids (βHAAs) into organic molecules has received considerable attention as these molecules have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of asymmetric synthesis of βHAAs, stereoselective synthesis to control the two chiral centres at C(α) and C(β) positions is still challenging, with poor atomic economy and multi protection and deprotection steps. These syntheses are often operated under harsh conditions. Therefore, a biotransformation approach using biocatalysts is needed to selectively introduce these two chiral centres into structurally diverse molecules. Yet, there are few ways that enable one-step synthesis of βHAAs. One is to extend the substrate scope of the existing enzyme inventory. Threonine aldolases have been explored to produce βHAAs. However, the enzymes have poor controlled installation at C(β) position, often resulting in a mixture of diastereoisomers which are difficult to be separated. In this respect, l-threonine transaldolases (LTTAs) offer an excellent potential as the enzymes often provide controlled stereochemistry at C(α) and C(β) positions. Another is to mine LTTA homologues and engineer the enzymes using directed evolution with the aim of finding engineered biocatalysts to accept broad substrates with enhanced conversion and stereoselectivity. Here, we review the development of LTTAs that incorporate various aldehyde acceptors to generate structurally diverse βHAAs and highlight areas for future developments. KEY POINTS: • The general mechanism of the transaldolation reaction catalysed by LTTAs • Recent advances in LTTAs from different biosynthetic pathways • Applications of LTTAs as biocatalysts for production of βHAAs Springer Berlin Heidelberg 2021-04-26 2021 /pmc/articles/PMC8072733/ /pubmed/33900425 http://dx.doi.org/10.1007/s00253-021-11288-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Mini-Review
Wang, Shan
Deng, Hai
Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids
title Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids
title_full Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids
title_fullStr Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids
title_full_unstemmed Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids
title_short Peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids
title_sort peculiarities of promiscuous l-threonine transaldolases for enantioselective synthesis of β-hydroxy-α-amino acids
topic Mini-Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072733/
https://www.ncbi.nlm.nih.gov/pubmed/33900425
http://dx.doi.org/10.1007/s00253-021-11288-w
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