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Synthetic chemistry provides an essential material basis for our clothing, food, housing, transportation, and medicine and is an important driving force for economic development. However, traditional chemical synthesis has bottleneck problems such as low efficiency and pollution.

Compared with traditional chemical synthesis, enzyme catalysis is more environmentally friendly and efficient. It has been widely used in the industrial production of functional molecules such as innovative drugs and has become an important alternative to conventional chemical synthesis methods.

Focusing on the biosynthesis of plant natural products and enzyme catalysis, the research group led by Prof. Lei Xiaoguang from Peking University's College of Chemistry and Molecular Engineering has yielded fruitful results in the discovery, mechanism study, and synthetic application of intermolecular Diels–Alderases (D–A).

Recently, the group was invited to publish their third , "Hunting for the Intermolecular Diels–Alderase," in the journal Accounts of Chemical Research.

As a cover article for the publication, the paper summarizes the research group's in-depth exploration in the field: it covers the biomimetic total synthesis of intermolecular D–A type natural products and how to utilize biomimetic synthesis and chemical proteomics to discover novel enzyme catalytic tools in plants, providing new insights for the study of plant natural product biosynthesis.

The article introduces the catalytic and natural evolution mechanisms of a novel intermolecular D–A enzyme in mulberry, offering crucial theoretical guidance for the rational discovery and modification of novel D–A enzymes.

Additionally, it proposes a diversity-oriented chemo-enzymatic synthesis strategy, integrating the advantages of decarboxylation functional group reactions and enzymatic D–A reactions, achieving efficient derivation and preparation of D–A products. This lays a significant material foundation for the drug development of D–A type natural products.