Biosynthesis of Quinolidomicin, the Largest Known Macrolide of Terrestrial Origin: Identification and Heterologous Expression of a Biosynthetic Gene Cluster over 200 kb

Takuya Hashimoto; Junko Hashimoto; Ikuko Kozone; Keita Amagai; Teppei Kawahara; Shunji Takahashi; Haruo Ikeda; Kazuo Shin-Ya

doi:10.1021/acs.orglett.8b03570

Biosynthesis of Quinolidomicin, the Largest Known Macrolide of Terrestrial Origin: Identification and Heterologous Expression of a Biosynthetic Gene Cluster over 200 kb

Org Lett. 2018 Dec 21;20(24):7996-7999. doi: 10.1021/acs.orglett.8b03570. Epub 2018 Dec 13.

Authors

Takuya Hashimoto¹, Junko Hashimoto², Ikuko Kozone², Keita Amagai^{3

4}, Teppei Kawahara², Shunji Takahashi⁴, Haruo Ikeda⁵, Kazuo Shin-Ya^{1

6}

Affiliations

¹ National Institute of Advanced Industrial Science and Technology , 2-4-7 Aomi , Koto-ku, Tokyo 135-0064 , Japan.
² Japan Biological Informatics Consortium , 2-4-7 Aomi , Koto-ku, Tokyo 135-0064 , Japan.
³ Technology Research Association for Next Generation Natural Products Chemistry , 2-4-7 Aomi , Koto-ku, Tokyo 135-0064 , Japan.
⁴ RIKEN Center for Sustainable Resource Science , Natural Product Biosynthesis Research Unit , 2-1 Hirosawa , Wako , Saitama 351-0198 , Japan.
⁵ Kitasato Institute for Life Sciences , Kitasato University , 1-15-1 Kitasato , Minami-ku, Sagamihara , Kanagawa 252-0373 , Japan.
⁶ The Biotechnology Research Center , The University of Tokyo , 1-1-1 Yayoi , Bunkyo-ku, Tokyo 113-8657 , Japan.

PMID: 30543302
DOI: 10.1021/acs.orglett.8b03570

Abstract

Quinolidomicin A₁ is the largest macrolide compound from terrestrial sources, consisting of a 60-membered ring, and its biosynthetic gene cluster was revealed to be over 200 kb. The gene cluster for quinolidomicin was cloned and heterologously expressed. Confirmation of the product led to a structural revision, in which the hydroxy group in the chromophore moiety of the reported structure was replaced by an amine group.

Publication types

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

MeSH terms

Anti-Bacterial Agents / biosynthesis*
Anti-Bacterial Agents / chemistry
Macrolides / chemistry
Macrolides / metabolism*
Molecular Conformation
Multigene Family
Streptomyces lividans / genetics*

Substances

Anti-Bacterial Agents
Macrolides
quinolidomicin A1