Revolutionizing enzyme engineering through artificial intelligence and machine learning

Abstract

The combinatorial space of an enzyme sequence has astronomical possibilities and exploring it with contemporary experimental techniques is arduous and often ineffective. Multi-target objectives such as concomitantly achieving improved selectivity, solubility and activity of an enzyme have narrow plausibility under approaches of restricted mutagenesis and combinatorial search. Traditional enzyme engineering approaches have a limited scope for complex optimization due to the requirement of a priori knowledge or experimental burden of screening huge protein libraries. The recent surge in high-throughput experimental methods including Next Generation Sequencing and automated screening has flooded the field of molecular biology with big-data, which requires us to re-think our concurrent approaches towards enzyme engineering. Artificial Intelligence (AI) and Machine Learning (ML) have great potential to revolutionize smart enzyme engineering without the explicit need for a complete understanding of the underlying molecular system. Here, we portray the role and position of AI techniques in the field of enzyme engineering along with their scope and limitations. In addition, we explain how the traditional approaches of directed evolution and rational design can be extended through AI tools. Recent successful examples of AI-assisted enzyme engineering projects and their deviation from traditional approaches are highlighted. A comprehensive picture of current challenges and future avenues for AI in enzyme engineering are also discussed.