Protein design drives synthetic biology research of plant natural products

Plant natural products (PNPs) are widely used in pharmaceutical, cosmetic, and food industries. Currently, their commercial supply largely relies on plant extraction, yet, suffers from low yield and limited resources. Synthetic biology provides a promising solution by reconstituting biosynthetic pathways of PNPs in microbial systems. However, unknown enzymatic steps or poor functional performance of plant-derived enzymes often make it particularly challenging for the PNPs production in microorganisms. To address these limitations, much progress has been made in enzyme mining, enzymatic mechanism elucidation, and enzyme optimization by protein design technologies. The deep integration of artificial intelligence and synthetic biology has provided attractive solutions for the sustainable production of PNPs. This review introduces the cutting-edge advances of protein design technologies in PNPs biosynthesis, elaborates on the approaches to resolve the main bottlenecks in PNPs biosynthesis, and discusses the immense application potential driven by the integration of AI and synthetic biology.