Manganese Transfer Hydrogenases Based on the Biotin-Streptavidin Technology.


Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
23 10 2023
Historique:
received: 15 08 2023
medline: 23 10 2023
pubmed: 6 9 2023
entrez: 6 9 2023
Statut: ppublish

Résumé

Artificial (transfer) hydrogenases have been developed for organic synthesis, but they rely on precious metals. Native hydrogenases use Earth-abundant metals, but these cannot be applied for organic synthesis due, in part, to their substrate specificity. Herein, we report the design and development of manganese transfer hydrogenases based on the biotin-streptavidin technology. By incorporating bio-mimetic Mn(I) complexes into the binding cavity of streptavidin, and through chemo-genetic optimization, we have obtained artificial enzymes that hydrogenate ketones with nearly quantitative yield and up to 98 % enantiomeric excess (ee). These enzymes exhibit broad substrate scope and high functional-group tolerance. According to QM/MM calculations and X-ray crystallography, the S112Y mutation, combined with the appropriate chemical structure of the Mn cofactor plays a critical role in the reactivity and enantioselectivity of the artificial metalloenzyme (ArMs). Our work highlights the potential of ArMs incorporating base-meal cofactors for enantioselective organic synthesis.

Identifiants

pubmed: 37671593
doi: 10.1002/anie.202311896
doi:

Substances chimiques

Biotin 6SO6U10H04
Streptavidin 9013-20-1
Hydrogenase EC 1.12.7.2
Manganese 42Z2K6ZL8P
Metalloproteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202311896

Informations de copyright

© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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Auteurs

Weijin Wang (W)

Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne ISIC-LSCI, BCH 3305, 1015, Lausanne, Switzerland.

Ryo Tachibana (R)

Department of Chemistry, University of Basel, Mattenstrasse 22, 4002, Basel, Switzerland.

Zhi Zou (Z)

Department of Chemistry, University of Basel, Mattenstrasse 22, 4002, Basel, Switzerland.

Dongping Chen (D)

Department of Chemistry, University of Basel, Mattenstrasse 22, 4002, Basel, Switzerland.

Xiang Zhang (X)

Department of Chemistry, University of Basel, Mattenstrasse 22, 4002, Basel, Switzerland.

Kelvin Lau (K)

Protein Production and Structure Core Facility (PTPSP), School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Florence Pojer (F)

Protein Production and Structure Core Facility (PTPSP), School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Thomas R Ward (TR)

Department of Chemistry, University of Basel, Mattenstrasse 22, 4002, Basel, Switzerland.
National Center of Competence in Research (NCCR) Catalysis, EPFL, 1015, Lausanne, Switzerland.

Xile Hu (X)

Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne ISIC-LSCI, BCH 3305, 1015, Lausanne, Switzerland.
National Center of Competence in Research (NCCR) Catalysis, EPFL, 1015, Lausanne, Switzerland.

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