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A chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism

Amide bond formation serves as a fundamental reaction in chemistry, and is practically useful for the synthesis of peptides, food additives, and polymers. However, current methods for amide bond formation essentially generate wastes and suffer from poor atom economy under harsh conditions. To solve...

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Detalles Bibliográficos
Autores principales: Hara, Ryotaro, Hirai, Kengo, Suzuki, Shin, Kino, Kuniki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811625/
https://www.ncbi.nlm.nih.gov/pubmed/29440726
http://dx.doi.org/10.1038/s41598-018-21408-8
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author Hara, Ryotaro
Hirai, Kengo
Suzuki, Shin
Kino, Kuniki
author_facet Hara, Ryotaro
Hirai, Kengo
Suzuki, Shin
Kino, Kuniki
author_sort Hara, Ryotaro
collection PubMed
description Amide bond formation serves as a fundamental reaction in chemistry, and is practically useful for the synthesis of peptides, food additives, and polymers. However, current methods for amide bond formation essentially generate wastes and suffer from poor atom economy under harsh conditions. To solve these issues, we demonstrated an alternative synthesis method for diverse tryptophyl-N-alkylamides by the combination of the first adenylation domain of tyrocidine synthetase 1 with primary or secondary amines as nucleophiles. Moreover, the physiological role of this domain is l-phenylalanine adenylation; however, we revealed that it displayed broad substrate flexibility from mono-substituted tryptophan analogues to even d-tryptophan. To the best of our knowledge, this is the first evidence for an adenylating enzyme-mediated direct amide bond formation via a sequential enzymatic activation of amino acids followed by nucleophilic substitution by general amines. These findings facilitate the design of a promising tool for biocatalytic straightforward amide bond formation with less side products.
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spelling pubmed-58116252018-02-16 A chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism Hara, Ryotaro Hirai, Kengo Suzuki, Shin Kino, Kuniki Sci Rep Article Amide bond formation serves as a fundamental reaction in chemistry, and is practically useful for the synthesis of peptides, food additives, and polymers. However, current methods for amide bond formation essentially generate wastes and suffer from poor atom economy under harsh conditions. To solve these issues, we demonstrated an alternative synthesis method for diverse tryptophyl-N-alkylamides by the combination of the first adenylation domain of tyrocidine synthetase 1 with primary or secondary amines as nucleophiles. Moreover, the physiological role of this domain is l-phenylalanine adenylation; however, we revealed that it displayed broad substrate flexibility from mono-substituted tryptophan analogues to even d-tryptophan. To the best of our knowledge, this is the first evidence for an adenylating enzyme-mediated direct amide bond formation via a sequential enzymatic activation of amino acids followed by nucleophilic substitution by general amines. These findings facilitate the design of a promising tool for biocatalytic straightforward amide bond formation with less side products. Nature Publishing Group UK 2018-02-13 /pmc/articles/PMC5811625/ /pubmed/29440726 http://dx.doi.org/10.1038/s41598-018-21408-8 Text en © The Author(s) 2018 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hara, Ryotaro
Hirai, Kengo
Suzuki, Shin
Kino, Kuniki
A chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism
title A chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism
title_full A chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism
title_fullStr A chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism
title_full_unstemmed A chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism
title_short A chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism
title_sort chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811625/
https://www.ncbi.nlm.nih.gov/pubmed/29440726
http://dx.doi.org/10.1038/s41598-018-21408-8
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