Elucidation of anthracyclinone biosynthesis by stepwise cloning of genes for anthracyclines from three different Streptomyces spp.
Elucidation of anthracyclinone biosynthesis by stepwise cloning of genes for anthracyclines from three different Streptomyces spp.
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DOI：
10.1099/00221287-146-1-155
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Mäntsälä, P
中科院分区：
文献类型：
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作者：
Kantola, J;Kunnari, T;Mäntsälä, P
通过芳香族(II型)聚酮合成酶生物合成了蒽环类化合物的骨架，而且还需要三步后聚酮反应才能形成蒽环类化合物的碱性苷元。在变铅青链霉菌中导入了来自3种不同产蒽环素的链霉菌的9个结构基因，构建金霉素生物合成簇的基因来源于新霉素。柔红霉素和阿克拉霉素产生链霉菌。生物合成阶段分为聚酮和聚酮后步骤，假设第一个稳定的中间体是新诺柳酸，类似于几种蒽环类药物的前体阿克兰酸。表达载体中的单基因按照所提出的生物合成途径决定的顺序被克隆，这有助于研究每个单独基因加入到构建体后在异源宿主中形成的产物，从而阐明生物合成步骤、产物和负责构建蒽环酮所需反应的基因。
The anthracycline skeleton is biosynthesized by aromatic (type II) polyketide synthases, Furthermore, three post-polyketide steps are needed to form the basic aglycone of anthracyclines. Auramycinone was produced in Streptomyces lividans by introducing nine structural genes from three different anthracycline-producing Streptomyces species, The genes used to construct the auramycinone biosynthesis cluster were derived from nogalamycin-. daunomycin- and aclacinomycin-producing Streptomyces strains. The biosynthetic stages were divided into polyketide and post-polyketide steps on the assumption that the first stable intermediate would be nogalonic acid, named analogously to aklanonic acid, the precursor of several anthracyclines. Single genes were cloned in the expression construct in the order determined by the proposed biosynthetic pathway, This facilitated investigation of the products formed in the heterologous host after addition of each separate gene to the construct, The results thus elucidate the biosynthesis steps, products and the genes responsible for the reactions needed to build up an anthracyclinone.