Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols

Voss, Moritz; Küng, Robin; Hayashi, Takahiro; Jonczyk, Magdalena; Niklaus, Michael; Iding, Hans; Wetzl, Dennis; Buller, Rebecca

doi:10.1002/cctc.202001871

Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-21381

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DC Field	Value	Language
dc.contributor.author	Voss, Moritz	-
dc.contributor.author	Küng, Robin	-
dc.contributor.author	Hayashi, Takahiro	-
dc.contributor.author	Jonczyk, Magdalena	-
dc.contributor.author	Niklaus, Michael	-
dc.contributor.author	Iding, Hans	-
dc.contributor.author	Wetzl, Dennis	-
dc.contributor.author	Buller, Rebecca	-
dc.date.accessioned	2021-01-21T13:59:20Z	-
dc.date.available	2021-01-21T13:59:20Z	-
dc.date.issued	2020-12	-
dc.identifier.issn	1867-3880	de_CH
dc.identifier.issn	1867-3899	de_CH
dc.identifier.uri	https://digitalcollection.zhaw.ch/handle/11475/21381	-
dc.description	This is the peer reviewed version which has been published in final form at https://doi.org/10.1002/cctc.202001871. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.	de_CH
dc.description.abstract	Enzymes are valuable tools to introduce chirality into small molecules. Especially, ketoreductase (KRED)‐catalyzed transformations of ketones to yield chiral secondary alcohols have become an established biocatalytic process step in the pharmaceutical and fine chemical industry. Development time, however, remains a critical factor in chemical process development and thus, the competitiveness of a biocatalytic reaction step is often governed by the availability of off‐the‐shelf enzyme libraries. To expand the biocatalytic toolbox with additional ketoreductases, we established a multi‐faceted screening procedure to capture KRED diversity from different sources, such as literature, available genome data, and uncharacterized microbial strains. Overall, we built a library consisting of 51 KRED enzymes, 29 of which have never been described in literature before. Notably, 18 of the newly described enzymes exhibited anti‐Prelog preference complementing the majority of ketoreductases which generally follow Prelog’s rule. Analysis of the library’s catalytic activity toward a chemically diverse ketone substrate set of pharmaceutical interest further highlighted the broad substrate scope and the complementing enantio‐preference of the individual KREDs. Using the generated sequence‐function data of the included short chain dehydrogenases in a bioinformatic analysis led to the identification of possible sequence determinants of the stereospecificity exhibited by these enzymes.	de_CH
dc.language.iso	en	de_CH
dc.publisher	Wiley	de_CH
dc.relation.ispartof	ChemCatChem	de_CH
dc.rights	Licence according to publishing contract	de_CH
dc.subject	Biocatalysis	de_CH
dc.subject	Ketoreductase	de_CH
dc.subject	Substrate scope	de_CH
dc.subject	Anti-Prelog stereoselectivity	de_CH
dc.subject	Multi-factorial screening	de_CH
dc.subject.ddc	660.6: Biotechnologie	de_CH
dc.title	Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols	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.202001871	de_CH
dc.identifier.doi	10.21256/zhaw-21381	-
zhaw.funding.eu	No	de_CH
zhaw.issue	6	de_CH
zhaw.originated.zhaw	Yes	de_CH
zhaw.pages.end	1545	de_CH
zhaw.pages.start	1538	de_CH
zhaw.publication.status	acceptedVersion	de_CH
zhaw.volume	13	de_CH
zhaw.embargo.end	2021-12-12	de_CH
zhaw.publication.review	Peer review (Publikation)	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., Küng, R., Hayashi, T., Jonczyk, M., Niklaus, M., Iding, H., Wetzl, D., & Buller, R. (2020). Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols. ChemCatChem, 13(6), 1538–1545. https://doi.org/10.1002/cctc.202001871

Voss, M. et al. (2020) ‘Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols’, ChemCatChem, 13(6), pp. 1538–1545. Available at: https://doi.org/10.1002/cctc.202001871.

M. Voss et al., “Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols,” ChemCatChem, vol. 13, no. 6, pp. 1538–1545, Dec. 2020, doi: 10.1002/cctc.202001871.

VOSS, Moritz, Robin KÜNG, Takahiro HAYASHI, Magdalena JONCZYK, Michael NIKLAUS, Hans IDING, Dennis WETZL und Rebecca BULLER, 2020. Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols. ChemCatChem. Dezember 2020. Bd. 13, Nr. 6, S. 1538–1545. DOI 10.1002/cctc.202001871

Voss, Moritz, Robin Küng, Takahiro Hayashi, Magdalena Jonczyk, Michael Niklaus, Hans Iding, Dennis Wetzl, and Rebecca Buller. 2020. “Multi‐Faceted Set‐up of a Diverse Ketoreductase Library Enables the Synthesis of Pharmaceutically‐Relevant Secondary Alcohols.” ChemCatChem 13 (6): 1538–45. https://doi.org/10.1002/cctc.202001871.

Voss, Moritz, et al. “Multi‐Faceted Set‐up of a Diverse Ketoreductase Library Enables the Synthesis of Pharmaceutically‐Relevant Secondary Alcohols.” ChemCatChem, vol. 13, no. 6, Dec. 2020, pp. 1538–45, https://doi.org/10.1002/cctc.202001871.