线性甘油酸盐是甲基氨酸生物合成中的糖转移酶DesVII的基质:分析和含义
Chai-Lin Kao1, Svetlana A Borisova, Hak Joong Kim
1Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, University of Texas, Austin, Texas 78712, USA.
Journal of the American Chemical Society
|April 28, 2006
概括
这项研究表明,宏类甘氨基转移酶可以处理线性多基基类前体,而不仅仅是循环的. 这扩大了对宏类抗生素生物合成途径的理解.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 抗生素合成 抗生素合成
背景情况:
- 宏类抗生素包括一个多基酸和糖.
- 阿格利康的合成由多基酸合成酶 (PKS) 介导,而糖化则由糖化转移酶介导.
- 已知糖化发生在aglycone循环和PKS释放后.
研究的目的:
- 调查宏类甘氨基转移酶是否可以处理与乙烯载体蛋白 (ACP) 结合的线性多基基前体.
- 探索宏类抗生素生物合成的替代途径.
主要方法:
- 线性aglycone前体,10-deoxymethynolide的化学合成,作为一个N-乙基胺 (NAC) .
- 合成的前体与TDP-d-desosamine,糖系转移酶DesVII和激活剂DesVIII的化.
- 使用高分辨率质谱分析反应产物的分析.
主要成果:
- 产生了更极性的产物,与线性前体的糖化相一致.
- 糖系转移酶DesVII成功处理了线性10-脱氧甲基诺化前体.
- 与循环基质相比,这种处理发生在减少但可测量的活性下.
结论:
- 宏类甘油转移酶可以识别和甘油化线性聚基酸前体.
- 这一发现扩大了在宏化物生物合成中已知的甘氨基转移酶的基质特异性.
- 这项研究为宏类抗生素组装途径的灵活性提供了新的见解.
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