Data-driven enzyme engineering to identify function-enhancing enzymes

Abstract

Abstract Identifying function-enhancing enzyme variants is a ‘holy grail’ challenge in protein science because it will allow researchers to expand the biocatalytic toolbox for late-stage functionalization of drug-like molecules, environmental degradation of plastics and other pollutants, and medical treatment of food allergies. Data-driven strategies, including statistical modeling, machine learning, and deep learning, have largely advanced the understanding of the sequence–structure–function relationships for enzymes. They have also enhanced the capability of predicting and designing new enzymes and enzyme variants for catalyzing the transformation of new-to-nature reactions. Here, we reviewed the recent progresses of data-driven models that were applied in identifying efficiency-enhancing mutants for catalytic reactions. We also discussed existing challenges and obstacles faced by the community. Although the review is by no means comprehensive, we hope that the discussion can inform the readers about the state-of-the-art in data-driven enzyme engineering, inspiring more joint experimental-computational efforts to develop and apply data-driven modeling to innovate biocatalysts for synthetic and pharmaceutical applications.