1Yunnan Key Laboratory of Potato Biology, The CAAS-YNNU-YINMORE Joint Academy of Potato Science, Yunnan Normal University, Yunnan, 650500, China
2State Key Laboratory of Tropical Crop Breeding, Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China
3National Key Laboratory of Crop Genetic Improvement and National Centre of Plant Gene Research, Huazhong Agricultural University, Wuhan, 430070, China
4Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02142, United States
5The authors have contributed equally to this work
| Received 01 Jul 2025 |
Accepted 15 Sep 2025 |
Published 30 Sep 2025 |
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.
