Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*

Voss, Moritz; Hüppi, Sean; Schaub, Daniela; Hayashi, Takahiro; Ligibel, Mathieu; Sager, Emine; Schroer, Kirsten; Snajdrova, Radka; Buller, Rebecca

doi:10.1002/cctc.202201115

Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-26366

Full metadata record

DC Field	Value	Language
dc.contributor.author	Voss, Moritz	-
dc.contributor.author	Hüppi, Sean	-
dc.contributor.author	Schaub, Daniela	-
dc.contributor.author	Hayashi, Takahiro	-
dc.contributor.author	Ligibel, Mathieu	-
dc.contributor.author	Sager, Emine	-
dc.contributor.author	Schroer, Kirsten	-
dc.contributor.author	Snajdrova, Radka	-
dc.contributor.author	Buller, Rebecca	-
dc.date.accessioned	2022-12-09T13:33:56Z	-
dc.date.available	2022-12-09T13:33:56Z	-
dc.date.issued	2022	-
dc.identifier.issn	1867-3880	de_CH
dc.identifier.issn	1867-3899	de_CH
dc.identifier.uri	https://digitalcollection.zhaw.ch/handle/11475/26366	-
dc.description.abstract	Enzymatic late-stage diversification of small molecules has the potential to rapidly generate diversity in compound libraries dedicated to drug discovery. In this context, freestanding Fe(II)/α-ketoglutarate-dependent halogenases have raised particular interest as this enzyme family allows the otherwise difficult regio- and stereoselective halogenation of unactivated C(sp3)-H bonds. Here, we report the development of two engineered variants of the halogenase WelO5* for the racemic resolution of a mixture of stereoisomers generated in the synthesis of a bioactive martinelline-derived fragment. By screening a 3-site combinatorial variant library, we could identify two variants exhibiting exquisite substrate selectivity towards the desired enantiomers. Strikingly, the inversion of substrate stereopreference between the halogenase variants was achieved by varying only three residues in the active site. Protein crystallization and subsequent structure elucidation of the wildtype enzyme and a WelO5* variant shed light on the factors governing substrate acceptance and selectivity.	de_CH
dc.language.iso	en	de_CH
dc.publisher	Wiley	de_CH
dc.relation.ispartof	ChemCatChem	de_CH
dc.rights	http://creativecommons.org/licenses/by/4.0/	de_CH
dc.subject	Biocatalysis	de_CH
dc.subject	Enzyme engineering	de_CH
dc.subject.ddc	660.6: Biotechnologie	de_CH
dc.title	Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*	de_CH
dc.type	Beitrag in wissenschaftlicher Zeitschrift	de_CH
dcterms.type	Text	de_CH
zhaw.departement	Life Sciences und Facility Management	de_CH
zhaw.organisationalunit	Institut für Chemie und Biotechnologie (ICBT)	de_CH
dc.identifier.doi	10.1002/cctc.202201115	de_CH
dc.identifier.doi	10.21256/zhaw-26366	-
zhaw.funding.eu	No	de_CH
zhaw.issue	24	de_CH
zhaw.originated.zhaw	Yes	de_CH
zhaw.pages.start	e202201115	de_CH
zhaw.publication.status	publishedVersion	de_CH
zhaw.volume	14	de_CH
zhaw.publication.review	Peer review (Publikation)	de_CH
zhaw.funding.snf	180544	de_CH
zhaw.webfeed	Biokatalyse	de_CH
zhaw.author.additional	No	de_CH
zhaw.display.portrait	Yes	de_CH
Appears in collections:	Publikationen Life Sciences und Facility Management

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Voss, M., Hüppi, S., Schaub, D., Hayashi, T., Ligibel, M., Sager, E., Schroer, K., Snajdrova, R., & Buller, R. (2022). Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*. ChemCatChem, 14(24), e202201115. https://doi.org/10.1002/cctc.202201115

Voss, M. et al. (2022) ‘Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*’, ChemCatChem, 14(24), p. e202201115. Available at: https://doi.org/10.1002/cctc.202201115.

M. Voss et al., “Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*,” ChemCatChem, vol. 14, no. 24, p. e202201115, 2022, doi: 10.1002/cctc.202201115.

VOSS, Moritz, Sean HÜPPI, Daniela SCHAUB, Takahiro HAYASHI, Mathieu LIGIBEL, Emine SAGER, Kirsten SCHROER, Radka SNAJDROVA und Rebecca BULLER, 2022. Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*. ChemCatChem. 2022. Bd. 14, Nr. 24, S. e202201115. DOI 10.1002/cctc.202201115

Voss, Moritz, Sean Hüppi, Daniela Schaub, Takahiro Hayashi, Mathieu Ligibel, Emine Sager, Kirsten Schroer, Radka Snajdrova, and Rebecca Buller. 2022. “Enzyme Engineering Enables Inversion of Substrate Stereopreference of the Halogenase WelO5*.” ChemCatChem 14 (24): e202201115. https://doi.org/10.1002/cctc.202201115.

Voss, Moritz, et al. “Enzyme Engineering Enables Inversion of Substrate Stereopreference of the Halogenase WelO5*.” ChemCatChem, vol. 14, no. 24, 2022, p. e202201115, https://doi.org/10.1002/cctc.202201115.