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

被引：3
作者：
Zhang, Mingge [1 ,2 ]
Shuang, Bao [3 ,4 ]
Arakawa, Kenji [1 ,2 ,3 ]
机构：
[1] Hiroshima Univ, Grad Sch Integrated Sci Life, 1-3-1 Kagamiyama, Higashihiroshima, Hiroshima 7398530, Japan
[2] Hiroshima Univ, Hiroshima Res Ctr Hlth Aging HiHA, 1-3-1 Kagamiyama, Higashihiroshima, Hiroshima 7398530, Japan
[3] Hiroshima Univ, Grad Sch Adv Sci Matter, Dept Mol Biotechnol, 1-3-1 Kagamiyama, Higashihiroshima, Hiroshima 7398530, Japan
[4] Northeast Agr Univ, Sch Life Sci, 600 Changjiang Rd, Harbin 150030, Heilongjiang, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2023年 / 80卷
基金：
日本学术振兴会;
关键词：
Macrolide; Biosynthesis; Deoxysugar; Branched; -chain; Streptomyces; GENE-CLUSTER; SIGNALING MOLECULES; D-DESOSAMINE; L-MYCAROSE; LANKACIDIN; IDENTIFICATION; SPECIFICITY; EXPRESSION; COMPLEX;
D O I：
10.1016/j.bmcl.2023.129125
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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.
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页数：7
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