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.
摘要：
兰卡霉素，一种由rochei链霉菌7434AN4产生的大环内酯类抗生素，表现出中等的抗菌活性，并通过与核糖体出口通道结合而与碳环抗生素lankacidinC协同作用。其生物合成基因（lkm）簇（orf24-orf53）位于最大的质粒pSLA2-L（210,614bp）上。我们的团队拥有多种兰卡霉素衍生物和大环内酯修饰酶，包括P450酶和糖基转移酶，这可能导致扩大生物活性大环内酯的化学库。在这里，我们构建了参与D-硫属糖生物合成的3-酮还原酶基因lkmCVI（orf42）的突变体，并对其代谢产物进行了分离和结构鉴定。具有支链脱氧糖的新型兰卡霉素衍生物的积累，5-O-(4\',6\'-二脱氧-3\'-C-乙酰基-D-核糖-己吡喃糖基)-3-O-(4\'-O-乙酰基-L-arcanosyl)-lankanolide,表明LkmCVI在兰卡霉素生物合成中充当D-硫属糖合成的门卫酶。
