Genome Mining-Based Discovery of Fungal Macrolides Modified by glycosylphosphatidylinositol (GPI)–Ethanolamine Phosphate Transferase Homologues

• DOI: 10.1021/acs.orglett.0c01975
• Publication Date: 2020-07-14T17:14:32Z
• Authors: Yohei Morishita; Yu Aoki; Mei Ito; Daisuke Hagiwara; Kensho Torimaru; Daichi Morita; Teruo Kuroda; Hanako Fukano; Yoshihiko Hoshino; Masato Suzuki; Tohru Taniguchi; Keiji Mori; Teigo Asai
• Keywords: Fungal Proteins; 0301 basic medicine; 03 medical and health sciences; Aspergillus; Molecular Structure; Ethanolamines; Glycosylphosphatidylinositols; Multigene Family; Protein Biosynthesis; Colletotrichum; Macrolides

Through genome mining for fungal macrolide natural products, we discovered a characteristic family of putative macrolide biosynthetic gene clusters that contain a glycosylphosphatidylinositol-ethanolamine phosphate transferase (GPI-EPT) homologue. Through the heterologous expression of two clusters from Aspergillus kawachii and Colletotrichum incanum, new macrolides, including those with phosphoethanolamine or phosphocholine moieties, were formed. This study is the first demonstration of the tailoring steps catalyzed by GPI-EPT homologues in natural product biosynthesis, and it uncovers a new gene resource for phospholipid-resembling fungal macrolides.