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Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase
[Image: see text] We report a chemo-biocatalytic cascade for the synthesis of substituted pyrroles, driven by the action of an irreversible, thermostable, pyridoxal 5′-phosphate (PLP)-dependent, C–C bond-forming biocatalyst (ThAOS). The ThAOS catalyzes the Claisen-like condensation between various a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10230504/ https://www.ncbi.nlm.nih.gov/pubmed/37266354 http://dx.doi.org/10.1021/acssuschemeng.3c00243 |
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author | Ashley, Ben Baslé, Arnaud Sajjad, Mariyah el Ashram, Ahmed Kelis, Panayiota Marles-Wright, Jon Campopiano, Dominic J. |
author_facet | Ashley, Ben Baslé, Arnaud Sajjad, Mariyah el Ashram, Ahmed Kelis, Panayiota Marles-Wright, Jon Campopiano, Dominic J. |
author_sort | Ashley, Ben |
collection | PubMed |
description | [Image: see text] We report a chemo-biocatalytic cascade for the synthesis of substituted pyrroles, driven by the action of an irreversible, thermostable, pyridoxal 5′-phosphate (PLP)-dependent, C–C bond-forming biocatalyst (ThAOS). The ThAOS catalyzes the Claisen-like condensation between various amino acids and acyl-CoA substrates to generate a range of α-aminoketones. These products are reacted with β-keto esters in an irreversible Knorr pyrrole reaction. The determination of the 1.6 Å resolution crystal structure of the PLP-bound form of ThAOS lays the foundation for future engineering and directed evolution. This report establishes the AOS family as useful and versatile C–C bond-forming biocatalysts. |
format | Online Article Text |
id | pubmed-10230504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-102305042023-06-01 Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase Ashley, Ben Baslé, Arnaud Sajjad, Mariyah el Ashram, Ahmed Kelis, Panayiota Marles-Wright, Jon Campopiano, Dominic J. ACS Sustain Chem Eng [Image: see text] We report a chemo-biocatalytic cascade for the synthesis of substituted pyrroles, driven by the action of an irreversible, thermostable, pyridoxal 5′-phosphate (PLP)-dependent, C–C bond-forming biocatalyst (ThAOS). The ThAOS catalyzes the Claisen-like condensation between various amino acids and acyl-CoA substrates to generate a range of α-aminoketones. These products are reacted with β-keto esters in an irreversible Knorr pyrrole reaction. The determination of the 1.6 Å resolution crystal structure of the PLP-bound form of ThAOS lays the foundation for future engineering and directed evolution. This report establishes the AOS family as useful and versatile C–C bond-forming biocatalysts. American Chemical Society 2023-05-16 /pmc/articles/PMC10230504/ /pubmed/37266354 http://dx.doi.org/10.1021/acssuschemeng.3c00243 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Ashley, Ben Baslé, Arnaud Sajjad, Mariyah el Ashram, Ahmed Kelis, Panayiota Marles-Wright, Jon Campopiano, Dominic J. Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase |
title | Versatile
Chemo-Biocatalytic Cascade Driven by a Thermophilic
and Irreversible C–C Bond-Forming α-Oxoamine Synthase |
title_full | Versatile
Chemo-Biocatalytic Cascade Driven by a Thermophilic
and Irreversible C–C Bond-Forming α-Oxoamine Synthase |
title_fullStr | Versatile
Chemo-Biocatalytic Cascade Driven by a Thermophilic
and Irreversible C–C Bond-Forming α-Oxoamine Synthase |
title_full_unstemmed | Versatile
Chemo-Biocatalytic Cascade Driven by a Thermophilic
and Irreversible C–C Bond-Forming α-Oxoamine Synthase |
title_short | Versatile
Chemo-Biocatalytic Cascade Driven by a Thermophilic
and Irreversible C–C Bond-Forming α-Oxoamine Synthase |
title_sort | versatile
chemo-biocatalytic cascade driven by a thermophilic
and irreversible c–c bond-forming α-oxoamine synthase |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10230504/ https://www.ncbi.nlm.nih.gov/pubmed/37266354 http://dx.doi.org/10.1021/acssuschemeng.3c00243 |
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