AN UNUSUALLY LARGE MULTIFUNCTIONAL POLYPEPTIDE IN THE ERYTHROMYCIN-PRODUCING POLYKETIDE SYNTHASE OF SACCHAROPOLYSPORA-ERYTHRAEA
AN UNUSUALLY LARGE MULTIFUNCTIONAL POLYPEPTIDE IN THE ERYTHROMYCIN-PRODUCING POLYKETIDE SYNTHASE OF SACCHAROPOLYSPORA-ERYTHRAEA
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DOI：
10.1038/348176a0
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发表时间：
1990-11-08
期刊：
影响因子：
64.8
通讯作者：
LEADLAY, PF
中科院分区：
文献类型：
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作者：
CORTES, J;HAYDOCK, SF;LEADLAY, PF
红霉素A是一种临床上重要的聚酮抗生素，由革兰氏阳性菌多孢菌产生。链霉菌和相关细菌中抗生素生物合成基因的排列似乎普遍如此。在拟南芥1中，编码红霉素生物合成途径的ery基因聚集在赋予S自身抗性的基因（ermE）周围。阿拉伯2 -6红霉素A的糖苷配基核心来源于一个丙酰辅酶A和六个甲基丙二酰辅酶A单元，这些单元在类似于脂肪酸生物合成1的过程中，首尾相连7 - 10地结合到生长中的聚酮链中，生成大环内酯中间体6-脱氧腺苷-罗丹明B10。6-脱氧红霉素B通过特异性羟化酶、糖基转移酶和甲基转移酶的作用2 -5，10转化为红霉素A。本文报道了10种S.通过从红霉素抗性决定子E向外的染色体“行走”克隆，并且先前显示对于红霉素生物合成是必需的5，11。该区域的部分测序表明它编码该合酶。我们的研究结果证实了这一点，并揭示了一种新的组织红霉素生产聚酮合酶，这提供了进一步深入了解链组装的机制。
ERYTHROMYCIN A, a clinically important polyketide antibiotic, is produced by the Gram-positive bacteriumSaccharopolyspora erythraea.. In an arrangement that seems to be generally true of antibiotic biosynthetic genes inStreptomycesand related bacteria likeS. erythraea1, the ery genes encoding the biosynthetic pathway to erythromvein are clustered around the gene (ermE) that confers self-resistance onS. erythraea2–6. The aglycone core of erythro-mycin A is derived from one propionyl-CoA and six methylmalonyl-CoA units, which are incorporated head-to-tail7–10into the growing polyketide chain, in a process similar to that of fatty-acid biosynthesis1, to generate a macrolide intermediate, 6-deoxyeryth-ronolide B10. 6-Deoxyerythronolide B is converted into erythro-mycin A through the action2–5,10of specific hydroxylases, glycosyItransferases and a methyltransferase. We report here the analysis of about 10 kilobases of DNA fromS. erythraea, cloned by chromosome 'walking' outwards from the erythromycin-resistance determinantermE, and previously shown to be essential for erythromycin biosynthesis5,11. Partial sequencing of this region12indicates that it encodes the synthase. Our results confirm this, and reveal a novel organization of the erythromycin-producing polyketide synthase, which provides further insight into the mechanism of chain assembly.