与抗肿瘤聚酮化合物光神霉素糖基生物合成最早步骤相关的泥质链霉菌基因的克隆及插入失活
Cloning and insertional inactivation of Streptomyces argillaceus genes involved in the earliest steps of biosynthesis of the sugar moieties of the antitumor polyketide mithramycin.
作者信息
Lombó F, Siems K, Braña A F, Méndez C, Bindseil K, Salas J A
机构信息
Departamento de Biología Funcional, Instituto Universitario de Biotecnología de Asturias (IUBA-CSIC), Universidad de Oviedo, Spain.
出版信息
J Bacteriol. 1997 May;179(10):3354-7. doi: 10.1128/jb.179.10.3354-3357.1997.
Abstract
Two genes (mtmD and mtmE) were cloned and sequenced from the mithramycin producer Streptomyces argillaceus. Comparison with proteins in databases and enzymatic assays after expression in Escherichia coli showed that they encode a glucose-1-phosphate:TTP thymidylyl transferase and a TDP-D-glucose 4,6-dehydratase, respectively. The mtmD gene was inactivated by gene replacement, generating a nonproducing mutant that accumulates a tetracyclic compound designated premithramycinone. The identification of premithramycinone reveals new aspects of the mithramycin biosynthetic pathway and suggests that at least some glycosylations occur before breakage of the fourth ring.
摘要
从光神霉素产生菌泥质链霉菌中克隆并测序了两个基因（mtmD和mtmE）。在大肠杆菌中表达后，与数据库中的蛋白质进行比较并进行酶活性测定，结果表明它们分别编码1-磷酸葡萄糖：TTP胸苷酰转移酶和TDP-D-葡萄糖4,6-脱水酶。通过基因置换使mtmD基因失活，产生了一个不产生光神霉素的突变体，该突变体积累了一种名为前光神霉素酮的四环化合物。前光神霉素酮的鉴定揭示了光神霉素生物合成途径的新方面，并表明至少一些糖基化反应发生在四环断裂之前。
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Cloning and insertional inactivation of Streptomyces argillaceus genes involved in the earliest steps of biosynthesis of the sugar moieties of the antitumor polyketide mithramycin.与抗肿瘤聚酮化合物光神霉素糖基生物合成最早步骤相关的泥质链霉菌基因的克隆及插入失活
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