Recent advances in the strategic use of multiple enzymatic transformations in the total synthesis of natural products

Coverage of selected chemoenzymatic natural product syntheses reported in the period 2021-2025Chemoenzymatic synthesis has emerged as a powerful strategy for the efficient construction and diversification of complex natural products by integrating the selectivity of biocatalysis with the flexibility of synthetic chemistry. This article surveys recent advances in utilization of multiple enzyme-enabled transformations that streamline key bond-forming and functionalization steps in natural product synthesis. Through selected case studies focusing on ATP-dependent ligases and oxidative enzymes, it is demonstrated how advances in protein engineering and genome mining have enabled efficient and selective transformations, thereby providing rapid access to natural products and their analogs across peptidic, polyketide, and terpene-derived scaffolds.