Systematic engineering of artificial metalloenzymes for new-to-nature reactions

Vornholt, Tobias and Christoffel, Fadri and Pellizzoni, Michela M. and Panke, Sven and Ward, Thomas R. and Jeschek, Markus. (2021) Systematic engineering of artificial metalloenzymes for new-to-nature reactions. Science Advances, 7 (4). eabe4208.

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Official URL: https://edoc.unibas.ch/83118/

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Artificial metalloenzymes (ArMs) catalyzing new-to-nature reactions could play an important role in transitioning toward a sustainable economy. While ArMs have been created for various transformations, attempts at their genetic optimization have been case specific and resulted mostly in modest improvements. To realize their full potential, methods to rapidly discover active ArM variants for ideally any reaction of interest are required. Here, we introduce a reaction-independent, automation-compatible platform, which relies on periplasmic compartmentalization in; Escherichia coli; to rapidly and reliably engineer ArMs based on the biotin-streptavidin technology. We systematically assess 400 ArM mutants for five bioorthogonal transformations involving different metals, reaction mechanisms, and reactants, which include novel ArMs for gold-catalyzed hydroamination and hydroarylation. Activity enhancements up to 15-fold highlight the potential of the systematic approach. Furthermore, we suggest smart screening strategies and build machine learning models that accurately predict ArM activity from sequence, which has crucial implications for future ArM development.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Bioanorganische Chemie (Ward)
UniBasel Contributors:Ward, Thomas R. R.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for the Advancement of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 May 2021 10:45
Deposited On:27 May 2021 10:45

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