Semi-synthesis of a DNA-Tagged Polyketide–Peptide Hybrid Macrocycle Using a Biosynthetically Prepared Fungal Macrolide as a Synthetic Component

Presented herein is a synthetic biological method using genome mining and heterologous expression systems that provides access to natural products with desirable structural features as building blocks. In this investigation, we synthesized polyketide-peptide hybrid macrocycles with DNA tags, which have the potential to access a DNA-encoded library containing over one million compounds. This study demonstrates that synthetic biology offers a tool for expanding the diversity of building blocks, facilitating the exploration of unexplored chemical space.