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Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Evolved aliphatic halogenases enable regiocomplementary C‐H functionalization of an added‐value chemical
Authors: Hayashi, Takahiro
Ligibel, Mathieu
Sager, Emine
Voss, Moritz
Hunziker, Jürg
Schroer, Kirsten
Snajdrova, Radka
Buller, Rebecca
et. al: No
DOI: 10.1002/anie.201907245
Published in: Angewandte Chemie: International Edition
Volume(Issue): 58
Issue: 51
Pages: 18535
Pages to: 18539
Issue Date: Oct-2019
Publisher / Ed. Institution: Wiley
ISSN: 1433-7851
Language: English
Subject (DDC): 660: Chemical engineering
Abstract: Non‐heme iron halogenases represent synthetically valuable biocatalysts that are capable of halogenating unactivated sp3‐hybridized carbon centers with exquisite stereo‐ and regioselectivity. The reported substrate scope of these enzymes, however, is limited primarily to the natural substrates and their analogues. Here we engineered the recently discovered halogenase WelO5* for chlorination of a pharmaceutically interesting martinelline‐derived fragment. Using structure‐guided evolution, a halogenase variant with a more than 290‐fold higher total turnover number and a 400‐fold higher apparent kcat compared to the wild‐type enzyme was generated. Moreover, we identified key positions in the active site which allowed directing the halogen to different positions in our target substrate. This report provides the first example of enzyme engineering to expand the substrate scope of a non‐heme iron halogenase beyond the native indole alkaloid‐type substrates. The highly evolvable nature of WelO5* underscores the usefulness of this enzyme family for the late‐stage halogenation of value‐added chemicals.
Further description: This is the peer reviewed version which has been published in final form at []. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Fulltext version: Accepted version
License (according to publishing contract): Licence according to publishing contract
Restricted until: 2020-10-31
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:Publikationen Life Sciences und Facility Management

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