Characterization of ty/M3/ty/M2 and mydC/mycB pairs required for efficient glycosyltransfer in macrolide antibiotic biosynthesis
Characterization of ty/M3/ty/M2 and mydC/mycB pairs required for efficient glycosyltransfer in macrolide antibiotic biosynthesis
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DOI：
10.1021/ja043900e
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发表时间：
2004-12-29
影响因子：
15
通讯作者：
Liu, HW
中科院分区：
文献类型：
--
作者：
Melancon, CE;Takahashi, H;Liu, HW
沿着两个功能未知的同源基因tylM 3和mydC以及编码它们各自的配偶体糖基转移酶tylM 2和mycB的基因和必需的糖生物合成基因的异源表达显著增强了工程化委内瑞拉链霉菌宿主中的糖基转移酶活性，其中天然糖基转移酶desVII已经失活。这两种糖基转移酶都接受内源性12元大环内酯，10-脱氧甲基炔雌醇，或外源性16元大环内酯，tylactone。使用该表达系统产生了五个新化合物。这项工作表明，在大环内酯类和蒽环类抗生素簇中发现的其他13种已知的TylM 3/MydC/DesVIII同源物也可能作为糖基转移酶辅助蛋白发挥作用。这些发现将极大地有助于以组合方式在这些途径中产生新的天然产物。
The heterologous expression oftylM3 andmydC, two homologous genes of previously unknown function, along with genes encoding their respective partner glycosyltransferases,tylM2 andmycB, and the necessary sugar biosynthesis genes significantly enhances the glycosyltransferase activity in the engineeredStreptomyces venezuelaehost in which the native glycosyltransferase,desVII, has been inactivated. Both glycosyltransferases accept the endogenous 12-membered macrolide, 10-deoxymethynolide, or the exogenously fed 16-membered macrolide, tylactone. Five new compounds were generated using this expression system. This work suggests that the 13 other known TylM3/MydC/DesVIII homologues found in macrolide and anthracycline antibiotic clusters likely function as glycosyltransferase auxiliary proteins as well. These findings will greatly assist endeavors to generate new natural products in these pathways in a combinatorial fashion.