Synzymes 2.0: Engineering catalytic function with artificial intelligence and advanced materials

The evolution of synthetic enzymes (synzymes) from simple biomimetic catalysts to sophisticated engineered systems represents a paradigm shift in biocatalysis. This comprehensive review provides a critical analysis of the current synzyme landscape, examining the strategic integration of artificial intelligence, nanotechnology, and synthetic biology in creating next-generation biocatalysts. We systematically evaluate three foundational pillars: (1) Rational Design Methodologies encompassing AI-driven prediction and high-throughput screening platforms; (2) Structural Innovation in scaffold development including metal-organic frameworks, DNA-based architectures, and hybrid biological-synthetic systems; and (3) Translational Applications across biomedical, industrial, and environmental sectors with specific emphasis on therapeutic efficacy, manufacturing scalability, and sustainability metrics. Our analytical framework assesses synzyme performance through comparative kinetic analysis (kcat/KM ratios), stability profiles under non-physiological conditions, and economic feasibility metrics. We identify critical research gaps in biocompatibility assessment, standardization protocols, and regulatory pathways while projecting future trajectories towards personalized catalytic therapeutics, autonomous bioremediation systems, and sustainable chemical manufacturing platforms. By integrating and critically reflecting on current advancements, this review constructs both a conceptual map and a strategic framework designed to guide the evolution of synzyme research from theoretical potential to real-world implementation.