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Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-23998
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dc.contributor.authorBüchler, Johannes-
dc.contributor.authorMalca, Sumire Honda-
dc.contributor.authorPatsch, David-
dc.contributor.authorVoss, Moritz-
dc.contributor.authorTurner, Nicholas J.-
dc.contributor.authorBornscheuer, Uwe T.-
dc.contributor.authorAllemann, Oliver-
dc.contributor.authorLe Chapelain, Camille-
dc.contributor.authorLumbroso, Alexandre-
dc.contributor.authorLoiseleur, Olivier-
dc.contributor.authorBuller, Rebecca-
dc.date.accessioned2022-01-27T14:49:37Z-
dc.date.available2022-01-27T14:49:37Z-
dc.date.issued2022-01-18-
dc.identifier.issn2041-1723de_CH
dc.identifier.urihttps://digitalcollection.zhaw.ch/handle/11475/23998-
dc.description.abstractLate-stage functionalization of natural products offers an elegant route to create novel entities in a relevant biological target space. In this context, enzymes capable of halogenating sp3 carbons with high stereo- and regiocontrol under benign conditions have attracted particular attention. Enabled by a combination of smart library design and machine learning, we engineer the iron/α-ketoglutarate dependent halogenase WelO5* for the late-stage functionalization of the complex and chemically difficult to derivatize macrolides soraphen A and C, potent anti-fungal agents. While the wild type enzyme WelO5* does not accept the macrolide substrates, our engineering strategy leads to active halogenase variants and improves upon their apparent kcat and total turnover number by more than 90-fold and 300-fold, respectively. Notably, our machine-learning guided engineering approach is capable of predicting more active variants and allows us to switch the regio-selectivity of the halogenases facilitating the targeted analysis of the derivatized macrolides’ structure-function activity in biological assays.de_CH
dc.language.isoende_CH
dc.publisherNature Publishing Groupde_CH
dc.relation.ispartofNature Communicationsde_CH
dc.rightshttp://creativecommons.org/licenses/by/4.0/de_CH
dc.subject.ddc660.6: Biotechnologiede_CH
dc.titleAlgorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphensde_CH
dc.typeBeitrag in wissenschaftlicher Zeitschriftde_CH
dcterms.typeTextde_CH
zhaw.departementLife Sciences und Facility Managementde_CH
zhaw.organisationalunitInstitut für Chemie und Biotechnologie (ICBT)de_CH
dc.identifier.doi10.1038/s41467-022-27999-1de_CH
dc.identifier.doi10.21256/zhaw-23998-
zhaw.funding.euNode_CH
zhaw.issue371de_CH
zhaw.originated.zhawYesde_CH
zhaw.publication.statuspublishedVersionde_CH
zhaw.volume13de_CH
zhaw.publication.reviewPeer review (Publikation)de_CH
zhaw.funding.snf180544de_CH
zhaw.webfeedBiokatalysede_CH
zhaw.funding.zhawPgB P-14 Engineered Halogenasesde_CH
zhaw.funding.zhawNCCR Catalysisde_CH
zhaw.author.additionalNode_CH
zhaw.display.portraitYesde_CH
Appears in collections:Publikationen Life Sciences und Facility Management

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Büchler, J., Malca, S. H., Patsch, D., Voss, M., Turner, N. J., Bornscheuer, U. T., Allemann, O., Le Chapelain, C., Lumbroso, A., Loiseleur, O., & Buller, R. (2022). Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens. Nature Communications, 13(371). https://doi.org/10.1038/s41467-022-27999-1
Büchler, J. et al. (2022) ‘Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens’, Nature Communications, 13(371). Available at: https://doi.org/10.1038/s41467-022-27999-1.
J. Büchler et al., “Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens,” Nature Communications, vol. 13, no. 371, Jan. 2022, doi: 10.1038/s41467-022-27999-1.
BÜCHLER, Johannes, Sumire Honda MALCA, David PATSCH, Moritz VOSS, Nicholas J. TURNER, Uwe T. BORNSCHEUER, Oliver ALLEMANN, Camille LE CHAPELAIN, Alexandre LUMBROSO, Olivier LOISELEUR und Rebecca BULLER, 2022. Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens. Nature Communications. 18 Januar 2022. Bd. 13, Nr. 371. DOI 10.1038/s41467-022-27999-1
Büchler, Johannes, Sumire Honda Malca, David Patsch, Moritz Voss, Nicholas J. Turner, Uwe T. Bornscheuer, Oliver Allemann, et al. 2022. “Algorithm-Aided Engineering of Aliphatic Halogenase WelO5* for the Asymmetric Late-Stage Functionalization of Soraphens.” Nature Communications 13 (371). https://doi.org/10.1038/s41467-022-27999-1.
Büchler, Johannes, et al. “Algorithm-Aided Engineering of Aliphatic Halogenase WelO5* for the Asymmetric Late-Stage Functionalization of Soraphens.” Nature Communications, vol. 13, no. 371, Jan. 2022, https://doi.org/10.1038/s41467-022-27999-1.


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