Science Advances: Systematic regulation of metalloenzymes to achieve novel enzyme catalytic activity

The artificial metalloenzyme ArMs can catalyze non-traditional reactions and play an important role in sustainable economy and development. Although ArMs enzymes with various reactions have been developed, the work on its genetic optimization is only in a few examples. Role, and only moderate improvement. In order to achieve further improvements, it is necessary to develop methods for rapid search of active ArM variants.



In view of this, ETH Zurich Markus Jeschek et al. reported a compatible automation platform that is suitable for various reaction conditions and can perform periplasmic separation of Escherichia coli through biotin-streptavidin technology. Rapidly engineer ArMs, through 5 kinds of bio-orthogonal transformations (including changing metals, reaction mechanisms, and reactants) to obtain 400 ArM variants, including novel Au catalysis that can be used for hydrogen amination and hydrogen arylation ArM.





Through this systematic engineering treatment, the activity is increased by 15 times, demonstrating the potential of this systematic optimization method. In addition, the author can accurately predict the activity of ArM through intelligent screening methods and machine learning models. This process is very helpful for the future development of ArM.







references

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

DOI: 10.1126/sciadv.abe4208

https://advances.sciencemag.org/content/7/4/eabe4208