Genome Mining-Based Discovery of Fungal Macrolides Modified by glycosylphosphatidylinositol (GPI)–Ethanolamine Phosphate Transferase Homologues
- Yohei MorishitaYohei MorishitaDepartment of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, JapanMore by Yohei Morishita
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- Yu AokiYu AokiDepartment of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, JapanMore by Yu Aoki
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- Mei ItoMei ItoTokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, JapanMore by Mei Ito
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- Daisuke HagiwaraDaisuke HagiwaraDepartment of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, JapanMicrobiology Research Center for Sustainability (MiCS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, JapanMore by Daisuke Hagiwara
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- Kensho TorimaruKensho TorimaruDepartment of Microbiology, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, JapanMore by Kensho Torimaru
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- Daichi MoritaDaichi MoritaDepartment of Microbiology, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, JapanMore by Daichi Morita
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- Teruo KurodaTeruo KurodaDepartment of Microbiology, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, JapanMore by Teruo Kuroda
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- Hanako FukanoHanako FukanoDepartment of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama-shi, Tokyo 189-0002, JapanMore by Hanako Fukano
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- Yoshihiko HoshinoYoshihiko HoshinoDepartment of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama-shi, Tokyo 189-0002, JapanMore by Yoshihiko Hoshino
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- Masato SuzukiMasato SuzukiAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama-shi, Tokyo 189-0002, JapanMore by Masato Suzuki
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- Tohru TaniguchiTohru TaniguchiFrontier Research Center for Advanced Material and Life Science, Faculty of Advanced Life Science, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, JapanMore by Tohru Taniguchi
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- Keiji MoriKeiji MoriDepartment of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, JapanMore by Keiji Mori
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- Teigo Asai*Teigo Asai*E-mail: [email protected]Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, JapanGraduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8578, JapanMore by Teigo Asai
Abstract

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.
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