Opportunities for merging biosynthesis and biocatalysis

Dongshan Wu, Jin Wang, Xiaoguang Lei Chem 12, October 8, 2026 https://doi.org/10.1016/j.chempr.2026.103254 The convergence of biosynthesis and biocatalysis is unlocking a new paradigm for the efficient construction of functional molecules, such as natural products and pharmaceuticals. By elucidating biosynthetic pathways, including all valuable enzymatic transformations that originate from biological systems, chemists can directly access powerful natural enzymes or engineer them via directed evolution to address long-standing synthetic challenges. This perspective explores the synergistic opportunities arising from integrating biosynthesis and biocatalysis. We highlight how enzymes derived from natural product biosynthetic pathways—such as Diels-Alderases—and tailored enzymes serve as powerful biocatalytic tools, with their utility further expanded through protein engineering. This convergence, by merging nature’s biosynthetic logic with modern chemo-catalytic concepts, enables new-to-nature reactivities. We further discuss how unmet synthetic demands are reshaping biosynthetic research, driving the discovery of enzymes with novel catalytic functions. We conclude by outlining future directions, including AI-driven enzyme discovery and engineering, as well as automated high-throughput experimentation, which will accelerate the translation of these integrating approaches into scalable and sustainable manufacturing solutions.

Dongshan Wu, Jin Wang, Xiaoguang Lei

Chem 12, October 8 (2026) 

https://doi.org/10.1016/j.chempr.2026.103254

The convergence of biosynthesis and biocatalysis is unlocking a new paradigm for the efficient construction of functional molecules, such as natural products and pharmaceuticals. By elucidating biosynthetic pathways, including all valuable enzymatic transformations that originate from biological systems, chemists can directly access powerful natural enzymes or engineer them via directed evolution to address long-standing synthetic challenges. This perspective explores the synergistic opportunities arising from integrating biosynthesis and biocatalysis. We highlight how enzymes derived from natural product biosynthetic pathways—such as Diels-Alderases—and tailored enzymes serve as powerful biocatalytic tools, with their utility further expanded through protein engineering. This convergence, by merging nature’s biosynthetic logic with modern chemo-catalytic concepts, enables new-to-nature reactivities. We further discuss how unmet synthetic demands are reshaping biosynthetic research, driving the discovery of enzymes with novel catalytic functions. We conclude by outlining future directions, including AI-driven enzyme discovery and engineering, as well as automated high-throughput experimentation, which will accelerate the translation of these integrating approaches into scalable and sustainable manufacturing solutions.