Publication

Enantioselective Synthesis of Pharmaceutically Active γ-Aminobutyric Acids Using a Tailor-Made Artificial Michaelase in One-Pot Cascade Reactions

Biewenga, L., Thangavelu, S., Kunzendorf, A., Van Der Meer, J., Pijning, T., Tepper, P., Van Merkerk, R., Charnock, S. J., Thunnissen, A. W. H. & Poelarends, G. J., 1-Feb-2019, In : ACS Catalysis. 9, p. 1503-1513 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Biewenga, L., Thangavelu, S., Kunzendorf, A., Van Der Meer, J., Pijning, T., Tepper, P., ... Poelarends, G. J. (2019). Enantioselective Synthesis of Pharmaceutically Active γ-Aminobutyric Acids Using a Tailor-Made Artificial Michaelase in One-Pot Cascade Reactions. ACS Catalysis, 9, 1503-1513. https://doi.org/10.1021/acscatal.8b04299

Author

Biewenga, Lieuwe ; Thangavelu, Saravanan ; Kunzendorf, Andreas ; Van Der Meer, Jan-ytzen ; Pijning, Tjaard ; Tepper, Pieter ; Van Merkerk, Ronald ; Charnock, Simon J. ; Thunnissen, Andy-mark W.h. ; Poelarends, Gerrit J. / Enantioselective Synthesis of Pharmaceutically Active γ-Aminobutyric Acids Using a Tailor-Made Artificial Michaelase in One-Pot Cascade Reactions. In: ACS Catalysis. 2019 ; Vol. 9. pp. 1503-1513.

Harvard

Biewenga, L, Thangavelu, S, Kunzendorf, A, Van Der Meer, J, Pijning, T, Tepper, P, Van Merkerk, R, Charnock, SJ, Thunnissen, AWH & Poelarends, GJ 2019, 'Enantioselective Synthesis of Pharmaceutically Active γ-Aminobutyric Acids Using a Tailor-Made Artificial Michaelase in One-Pot Cascade Reactions', ACS Catalysis, vol. 9, pp. 1503-1513. https://doi.org/10.1021/acscatal.8b04299

Standard

Enantioselective Synthesis of Pharmaceutically Active γ-Aminobutyric Acids Using a Tailor-Made Artificial Michaelase in One-Pot Cascade Reactions. / Biewenga, Lieuwe; Thangavelu, Saravanan; Kunzendorf, Andreas; Van Der Meer, Jan-ytzen; Pijning, Tjaard; Tepper, Pieter; Van Merkerk, Ronald; Charnock, Simon J.; Thunnissen, Andy-mark W.h.; Poelarends, Gerrit J.

In: ACS Catalysis, Vol. 9, 01.02.2019, p. 1503-1513.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Biewenga L, Thangavelu S, Kunzendorf A, Van Der Meer J, Pijning T, Tepper P et al. Enantioselective Synthesis of Pharmaceutically Active γ-Aminobutyric Acids Using a Tailor-Made Artificial Michaelase in One-Pot Cascade Reactions. ACS Catalysis. 2019 Feb 1;9:1503-1513. https://doi.org/10.1021/acscatal.8b04299


BibTeX

@article{dd72f9b5d0014ba8acb8993313a48391,
title = "Enantioselective Synthesis of Pharmaceutically Active γ-Aminobutyric Acids Using a Tailor-Made Artificial Michaelase in One-Pot Cascade Reactions",
abstract = "Chiral γ-aminobutyric acid (GABA) analogues represent abundantly prescribed drugs, which are broadly applied as anticonvulsants, antidepressants and for the treatment of neuropathic pain. Here we report a one-pot two-step biocatalytic cascade route for synthesis of the pharmaceutically relevant enantiomers of γ-nitrobutyric acids, starting from simple precursors (acetaldehyde and nitroalkenes), using a tailor-made highly enantioselective artificial ‘Michaelase’ (4-oxalocrotonate tautomerase mutant L8Y/M45Y/F50A), an aldehyde dehydrogenase with a broad non-natural substrate scope, and a cofactor recycling system. We also report a three-step chemoenzymatic cascade route for the efficient chemical reduction of enzymatically prepared γ-nitrobutyric acids into GABA analogues in one pot, achieving high enantiopurity (e.r. up to 99:1) and high overall yields (up to 70{\%}). This chemoenzymatic methodology offers a step-economic alternative route to important pharmaceutically active GABA analogues, and highlights the exciting opportunities available for combining chemocatalysts, natural enzymes, and designed artificial biocatalysts in multistep syntheses.",
keywords = "Systems biocatalysis, cascades, {"}Michaelase{"}, gamma-aminobutyric acids, gamma-nitrobutyric acids, enzyme engineering, pharmaceuticals, 4-OXALOCROTONATE TAUTOMERASE, MUTABILITY LANDSCAPES, ADDITION-REACTIONS, CATALYSIS, ACETALDEHYDE, REDUCTION, ALDEHYDES",
author = "Lieuwe Biewenga and Saravanan Thangavelu and Andreas Kunzendorf and {Van Der Meer}, Jan-ytzen and Tjaard Pijning and Pieter Tepper and {Van Merkerk}, Ronald and Charnock, {Simon J.} and Thunnissen, {Andy-mark W.h.} and Poelarends, {Gerrit J.}",
year = "2019",
month = "2",
day = "1",
doi = "10.1021/acscatal.8b04299",
language = "English",
volume = "9",
pages = "1503--1513",
journal = "ACS Catalysis",
issn = "2155-5435",
publisher = "AMER CHEMICAL SOC",

}

RIS

TY - JOUR

T1 - Enantioselective Synthesis of Pharmaceutically Active γ-Aminobutyric Acids Using a Tailor-Made Artificial Michaelase in One-Pot Cascade Reactions

AU - Biewenga, Lieuwe

AU - Thangavelu, Saravanan

AU - Kunzendorf, Andreas

AU - Van Der Meer, Jan-ytzen

AU - Pijning, Tjaard

AU - Tepper, Pieter

AU - Van Merkerk, Ronald

AU - Charnock, Simon J.

AU - Thunnissen, Andy-mark W.h.

AU - Poelarends, Gerrit J.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Chiral γ-aminobutyric acid (GABA) analogues represent abundantly prescribed drugs, which are broadly applied as anticonvulsants, antidepressants and for the treatment of neuropathic pain. Here we report a one-pot two-step biocatalytic cascade route for synthesis of the pharmaceutically relevant enantiomers of γ-nitrobutyric acids, starting from simple precursors (acetaldehyde and nitroalkenes), using a tailor-made highly enantioselective artificial ‘Michaelase’ (4-oxalocrotonate tautomerase mutant L8Y/M45Y/F50A), an aldehyde dehydrogenase with a broad non-natural substrate scope, and a cofactor recycling system. We also report a three-step chemoenzymatic cascade route for the efficient chemical reduction of enzymatically prepared γ-nitrobutyric acids into GABA analogues in one pot, achieving high enantiopurity (e.r. up to 99:1) and high overall yields (up to 70%). This chemoenzymatic methodology offers a step-economic alternative route to important pharmaceutically active GABA analogues, and highlights the exciting opportunities available for combining chemocatalysts, natural enzymes, and designed artificial biocatalysts in multistep syntheses.

AB - Chiral γ-aminobutyric acid (GABA) analogues represent abundantly prescribed drugs, which are broadly applied as anticonvulsants, antidepressants and for the treatment of neuropathic pain. Here we report a one-pot two-step biocatalytic cascade route for synthesis of the pharmaceutically relevant enantiomers of γ-nitrobutyric acids, starting from simple precursors (acetaldehyde and nitroalkenes), using a tailor-made highly enantioselective artificial ‘Michaelase’ (4-oxalocrotonate tautomerase mutant L8Y/M45Y/F50A), an aldehyde dehydrogenase with a broad non-natural substrate scope, and a cofactor recycling system. We also report a three-step chemoenzymatic cascade route for the efficient chemical reduction of enzymatically prepared γ-nitrobutyric acids into GABA analogues in one pot, achieving high enantiopurity (e.r. up to 99:1) and high overall yields (up to 70%). This chemoenzymatic methodology offers a step-economic alternative route to important pharmaceutically active GABA analogues, and highlights the exciting opportunities available for combining chemocatalysts, natural enzymes, and designed artificial biocatalysts in multistep syntheses.

KW - Systems biocatalysis

KW - cascades

KW - "Michaelase"

KW - gamma-aminobutyric acids

KW - gamma-nitrobutyric acids

KW - enzyme engineering

KW - pharmaceuticals

KW - 4-OXALOCROTONATE TAUTOMERASE

KW - MUTABILITY LANDSCAPES

KW - ADDITION-REACTIONS

KW - CATALYSIS

KW - ACETALDEHYDE

KW - REDUCTION

KW - ALDEHYDES

U2 - 10.1021/acscatal.8b04299

DO - 10.1021/acscatal.8b04299

M3 - Article

VL - 9

SP - 1503

EP - 1513

JO - ACS Catalysis

JF - ACS Catalysis

SN - 2155-5435

ER -

ID: 73806279