Accumulation of lankamycin derivative with a branched-chain sugar from a blocked mutant of chalcose biosynthesis in Streptomyces rochei 7434AN4

Mingge Zhang; Bao Shuang; Kenji Arakawa

doi:10.1016/j.bmcl.2023.129125

Accumulation of lankamycin derivative with a branched-chain sugar from a blocked mutant of chalcose biosynthesis in Streptomyces rochei 7434AN4

Bioorg Med Chem Lett. 2023 Jan 15:80:129125. doi: 10.1016/j.bmcl.2023.129125. Epub 2023 Jan 5.

Authors

Mingge Zhang¹, Bao Shuang², Kenji Arakawa³

Affiliations

¹ Graduate School of Integrated Sciences for Life, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan; Hiroshima Research Center for Healthy Aging (HiHA), Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan.
² Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan; School of Life Sciences, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, Heilongjiang 150030, China.
³ Graduate School of Integrated Sciences for Life, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan; Hiroshima Research Center for Healthy Aging (HiHA), Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan; Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan. Electronic address: karakawa@hiroshima-u.ac.jp.

PMID: 36621553
DOI: 10.1016/j.bmcl.2023.129125

Abstract

Lankamycin, a macrolide antibiotic produced by Streptomyces rochei 7434AN4, exhibits a moderate antimicrobial activity and acts as a synergistic pair with carbocyclic antibiotic lankacidin C by binding to the ribosome exit tunnel. Its biosynthetic gene (lkm) cluster (orf24-orf53) is located on the largest plasmid pSLA2-L (210,614 bp). Our group possesses a variety of lankamycin derivatives and macrolide-modification enzymes including P450 enzymes and glycosyltransferases, which may lead to expand the chemical library of bioactive macrolides. Here we constructed a mutant of a 3-ketoreductase gene lkmCVI (orf42) involved in d-chalcose biosynthesis, and its metabolite was isolated and structure-elucidated. Accumulation of novel lankamycin derivative harboring a branched-chain deoxysugar, 5-O-(4',6'-dideoxy-3'-C-acetyl-d-ribo-hexopyranosyl)-3-O-(4″-O-acetyl-l-arcanosyl)-lankanolide, indicated that LkmCVI acts as a gate keeper enzyme for d-chalcose synthesis in lankamycin biosynthesis.

Keywords: Biosynthesis; Branched-chain; Deoxysugar; Macrolide; Streptomyces.

Publication types

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

MeSH terms

Anti-Bacterial Agents* / pharmacology
Macrolides / pharmacology
Multigene Family
Sugars*

Substances

kujimycin B
Sugars
Anti-Bacterial Agents
Macrolides

Supplementary concepts

Streptomyces rochei