Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ashley, Ben, Baslé, Arnaud, Sajjad, Mariyah, el Ashram, Ahmed, Kelis, Panayiota, Marles-Wright, Jon, Campopiano, Dominic J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
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
_version_ 1785051546321420288
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
work_keys_str_mv AT ashleyben versatilechemobiocatalyticcascadedrivenbyathermophilicandirreversibleccbondformingaoxoaminesynthase
AT baslearnaud versatilechemobiocatalyticcascadedrivenbyathermophilicandirreversibleccbondformingaoxoaminesynthase
AT sajjadmariyah versatilechemobiocatalyticcascadedrivenbyathermophilicandirreversibleccbondformingaoxoaminesynthase
AT elashramahmed versatilechemobiocatalyticcascadedrivenbyathermophilicandirreversibleccbondformingaoxoaminesynthase
AT kelispanayiota versatilechemobiocatalyticcascadedrivenbyathermophilicandirreversibleccbondformingaoxoaminesynthase
AT marleswrightjon versatilechemobiocatalyticcascadedrivenbyathermophilicandirreversibleccbondformingaoxoaminesynthase
AT campopianodominicj versatilechemobiocatalyticcascadedrivenbyathermophilicandirreversibleccbondformingaoxoaminesynthase