Analysis of the Tunicamycin Biosynthetic Gene Cluster of Streptomyces chartreusis Reveals New Insights into Tunicamycin Production and Immunity.
Analysis of the Tunicamycin Biosynthetic Gene Cluster of Streptomyces chartreusis Reveals New Insights into Tunicamycin Production and Immunity.
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DOI：
10.1128/aac.00130-18
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发表时间：
2018-08
影响因子：
4.9
通讯作者：
Bibb MJ
中科院分区：
文献类型：
--
作者：
Widdick D;Royer SF;Wang H;Vior NM;Gomez-Escribano JP;Davis BG;Bibb MJ
黄曲霉链霉菌的衣霉素生物合成基因簇由 14 个基因（tunA 至 tunN）组成，具有高度的明显翻译耦合。转录分析表明，所有这些基因都可能从两个启动子 tunp1 和 tunp2 转录为单个操纵子。框内删除分析显示，其中只有 6 个基因 (tunABCDEH) 对于异源宿主天蓝色链霉菌中衣霉素的生产是必需的，而在初级代谢中可能对应的 5 个基因 (tunFGKLN) 不是必需的，但可能确保在衣霉素生物合成开始时有效生产抗生素。三个基因与免疫有关，即 tunI 和 tunJ，它们编码可能是抗生素输出所需的双组分 ABC 转运蛋白；以及 tunM，它编码假定的 S-腺苷甲硫氨酸 (SAM) 依赖性甲基转移酶。天蓝色链球菌中 tunIJ 或 tunM 的表达赋予了对外源衣霉素的抗性。这里提出的结果为衣霉素生物合成和免疫提供了新的见解。
The tunicamycin biosynthetic gene cluster of Streptomyces chartreusis consists of 14 genes (tunA to tunN) with a high degree of apparent translational coupling. Transcriptional analysis revealed that all of these genes are likely to be transcribed as a single operon from two promoters, tunp1 and tunp2. In-frame deletion analysis revealed that just six of these genes (tunABCDEH) are essential for tunicamycin production in the heterologous host Streptomyces coelicolor, while five (tunFGKLN) with likely counterparts in primary metabolism are not necessary, but presumably ensure efficient production of the antibiotic at the onset of tunicamycin biosynthesis. Three genes are implicated in immunity, namely, tunI and tunJ, which encode a two-component ABC transporter presumably required for export of the antibiotic, and tunM, which encodes a putative S-adenosylmethionine (SAM)-dependent methyltransferase. Expression of tunIJ or tunM in S. coelicolor conferred resistance to exogenous tunicamycin. The results presented here provide new insights into tunicamycin biosynthesis and immunity.