Semi-synthesis\nof a DNA-Tagged Polyketide–Peptide\nHybrid Macrocycle Using a Biosynthetically Prepared Fungal Macrolide\nas a Synthetic Component

Presented herein is a synthetic biological method using\ngenome\nmining and heterologous expression systems that provides access to\nnatural products with desirable structural features as building blocks.\nIn this investigation, we synthesized polyketide–peptide hybrid\nmacrocycles with DNA tags, which have the potential to access a DNA-encoded\nlibrary containing over one million compounds. This study demonstrates\nthat synthetic biology offers a tool for expanding the diversity of\nbuilding blocks, facilitating the exploration of unexplored chemical\nspace.