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

Bioorganic & medicinal chemistry letters 2023 Jan 15

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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. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Mingge Zhang, Bao Shuang, Kenji Arakawa. Accumulation of lankamycin derivative with a branched-chain sugar from a blocked mutant of chalcose biosynthesis in Streptomyces rochei 7434AN4. Bioorganic & medicinal chemistry letters. 2023 Jan 15;80:129125