The Discovery of Fungal Polyene Macrolides via a Postgenomic Approach Reveals a Polyketide Macrocyclization by trans-Acting Thioesterase in Fungi

Yohei Morishita; Huiping Zhang; Tohru Taniguchi; Keiji Mori; Teigo Asai

doi:10.1021/acs.orglett.9b01674

The Discovery of Fungal Polyene Macrolides via a Postgenomic Approach Reveals a Polyketide Macrocyclization by trans-Acting Thioesterase in Fungi

Org Lett. 2019 Jun 21;21(12):4788-4792. doi: 10.1021/acs.orglett.9b01674. Epub 2019 Jun 10.

Authors

Yohei Morishita¹, Huiping Zhang², Tohru Taniguchi³, Keiji Mori⁴, Teigo Asai¹

Affiliations

¹ Department of Life Sciences, Graduate School of Arts and Sciences , The University of Tokyo , 3-8-1 Komaba , Meguro-ku, Tokyo 153-8902 , Japan.
² NMR Science and Development Division , RIKEN Spring-8 Center , 1-7-22 Suehiro-cho , Tsurumi-ku, Yokohama , Kanagawa 230-0045 , Japan.
³ Faculty of Advanced Life Science, Frontier Research Center for Post-Genome Science and Technology , Hokkaido University , Kita 21 Nishi 11 , Sapporo 001-0021 , Japan.
⁴ Department of Applied Chemistry, Graduate School of Engineering , Tokyo University of Agriculture and Technology , 2-24-16 Nakacho , Koganei, Tokyo 184-8588 , Japan.

PMID: 31180682
DOI: 10.1021/acs.orglett.9b01674

Abstract

Heterologous expression of a unique biosynthetic gene cluster (BGC) comprising a highly reducing polyketide synthase and stand-alone thioesterase genes in Aspergillus oryzae enabled us to isolate a novel 34-membered polyene macrolide, phaeospelide A (1). This is the first isolation of a fungal polyene macrolide and the first demonstration of fungal aliphatic macrolide biosynthetic machinery. In addition, sequence similarity network analysis demonstrated the existence of a large number of BGCs for novel fungal macrolides.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aspergillus oryzae / enzymology
Cyclization
Macrolides / chemistry
Macrolides / isolation & purification
Macrolides / metabolism*
Molecular Conformation
Polyenes / chemistry
Polyenes / isolation & purification
Polyenes / metabolism*
Polyketides / chemistry
Polyketides / metabolism*
Thiolester Hydrolases / genetics
Thiolester Hydrolases / metabolism*
Trans-Activators / chemistry
Trans-Activators / metabolism*

Substances

Macrolides
Polyenes
Polyketides
Trans-Activators
Thiolester Hydrolases