Chemoenzymatic approaches for exploring structure-activity relationship studies of bioactive natural products

Spurred by advancements in microbial genetics and enzyme engineering, chemoenzymatic strategies, which combine enzymatic and synthetic transformations, have increasingly made an impact in the synthesis of bioactive natural products, pharmaceutical components and other valuable molecules. Beyond target-oriented synthesis, researchers have also leveraged chemoenzymatic approaches in structure-activity relationship (SAR) studies of bioactive natural products by using enzymatic reactions in either the early-stage construction of key building blocks or the late-stage modification of key intermediates. This Review summarizes the applications of chemoenzymatic approaches for SAR exploration of natural products, categorizing the case studies according to the stage in which the enzymatic reactions are performed. Current challenges in the field are also discussed, along with emerging technologies that may provide solutions to these challenges in the future. Chemoenzymatic strategies that combine chemical and enzymatic transformations are becoming increasingly popular in the synthesis of complex molecules. This Review highlights notable case studies in the application of chemoenzymatic strategies for structure-activity relationship explorations of bioactive natural products.