Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase

Ben Ashley; Arnaud Baslé; Mariyah Sajjad; Ahmed El ashram; Panayiota Kelis; Jon Marles-Wright; Dominic J. Campopiano

doi:10.1021/acssuschemeng.3c00243

Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase

Ben Ashley, Arnaud Baslé, Mariyah Sajjad, Ahmed El ashram, Panayiota Kelis, Jon Marles-Wright, Dominic J. Campopiano

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Journal	ACS Sustainable Chemistry & Engineering
Early online date	16 May 2023
DOIs	https://doi.org/10.1021/acssuschemeng.3c00243
Publication status	E-pub ahead of print - 16 May 2023

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10.1021/acssuschemeng.3c00243

20230516Campopianoacssuschemeng.3c00243VoRFinal published version, 2.24 MBLicence: Creative Commons: Attribution (CC-BY)

https://pubs.acs.org/doi/10.1021/acssuschemeng.3c00243

EASTBIO: EASTBIO East of Scotland BioScience Doctoral Training Partnership studentship - Research Training Grant BB/J01446X/1
Smith, S.
1/09/12 → 30/09/18
Project: Other (Non-Funded/Miscellaneous)

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@article{d2808b3e21c34a16847ee65ba8602c5c,

title = "Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase",

abstract = "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 {\AA} 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.",

author = "Ben Ashley and Arnaud Basl{\'e} and Mariyah Sajjad and {El ashram}, Ahmed and Panayiota Kelis and Jon Marles-Wright and Campopiano, {Dominic J.}",

note = "Funding Information: We thank Diamond Light Source for beamtime (mx 24948) and the staff of beamline I03. Thanks to Alan Taylor and Michael Herrera for help in mass spectrometry analysis. B.A. thanks the BBSRC EastBio DTP (BB/J01446X/1) for funding. M.S. thanks The Derek Stewart Charitable Trust for funding. Publisher Copyright: {\textcopyright} 2023 The Authors. Published by American Chemical Society.",

year = "2023",

month = may,

day = "16",

doi = "10.1021/acssuschemeng.3c00243",

language = "English",

journal = "ACS Sustainable Chemistry & Engineering",

issn = "2168-0485",

publisher = "American Chemical Society",

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T1 - Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase

AU - Ashley, Ben

AU - Baslé, Arnaud

AU - Sajjad, Mariyah

AU - El ashram, Ahmed

AU - Kelis, Panayiota

AU - Marles-Wright, Jon

AU - Campopiano, Dominic J.

N1 - Funding Information: We thank Diamond Light Source for beamtime (mx 24948) and the staff of beamline I03. Thanks to Alan Taylor and Michael Herrera for help in mass spectrometry analysis. B.A. thanks the BBSRC EastBio DTP (BB/J01446X/1) for funding. M.S. thanks The Derek Stewart Charitable Trust for funding. Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.

PY - 2023/5/16

Y1 - 2023/5/16

N2 - 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.

AB - 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.

U2 - 10.1021/acssuschemeng.3c00243

DO - 10.1021/acssuschemeng.3c00243

M3 - Article

SN - 2168-0485

JO - ACS Sustainable Chemistry & Engineering

JF - ACS Sustainable Chemistry & Engineering

ER -

Versatile Chemo-Biocatalytic Cascade Driven by a Thermophilic and Irreversible C–C Bond-Forming α-Oxoamine Synthase

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Projects

EASTBIO: EASTBIO East of Scotland BioScience Doctoral Training Partnership studentship - Research Training Grant BB/J01446X/1

Cite this