Accumulation of lankamycin derivative with a branched-chain sugar from a blocked mutant of chalcose biosynthesis in Streptomyces rochei 7434AN4. (15th January 2023)

• Record Type: Journal Article
• Authors: Zhang, Mingge; Shuang, Bao; Arakawa, Kenji
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 80(2023)
• Publication Date: 2023-01-15
• Subjects: Macrolide -- Biosynthesis -- Deoxysugar -- Branched-chain -- Streptomyces; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2023.129125
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.