The third wave of enzyme engineering: Navigating the AI-powered IDEA paradigm

Abstract

Enzyme engineering has evolved from random directed evolution to knowledge-guided rational design and is now entering an artificial intelligence (AI)-driven third wave. To capture AI’s transformative impact, we propose the investigate-design-execute-analyze (IDEA) framework, which illustrates how AI integrates across the entire enzyme engineering pipeline—from enzyme discovery and biocatalyst design to experimental validation and mechanistic analysis. This framework serves as a roadmap for leveraging advanced AI to reprogram enzyme engineering workflows, establishing a new paradigm for intelligent biocatalyst design.