在宝米生物合成中,由酸合成酶触发的氧化碳-碳键裂变
Ahmad Al-Mestarihi1, Anthony Romo, Hung-wen Liu
1Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, USA.
Journal of the American Chemical Society
|July 27, 2013
概括
米辛与抗癌药物鲁素和多鲁素相关,具有不寻常的糖分. DnmZ酶通过一种新的逆氧胺-阿尔多尔反应启动它们独特的生物合成.
科学领域:
- 生物化学 生物化学
- 微生物学 微生物学
- 自然产品的合成自然产品的合成
背景情况:
- 宝米辛与诺鲁比辛和多克索鲁比辛共同生产,这是来自*Streptomyces peucetius*的重要抗癌类人类循环素.
- 宝米辛在索胺糖上拥有独特的乙基,在标准提取过程中丢失.
- 这种乙表明它来自一个不寻常的分支脱氧糖.
研究的目的:
- 为了阐明宝米辛中不寻常的糖分的生物合成途径.
- 描述宝米/达努鲁比生物合成基因群中的*dnmZ*基因的功能.
- 调查启动新型糖改性的酶机制.
主要方法:
- 对*dox*基因集群的生物信息分析,重点是*dnmZ*.
- 将DnmZ与已知的酶,特别是化酶的序列相似性进行比较.
- 生物化学测试以确定DnmZ在糖基板上的酶活性.
主要成果:
- *dnmZ*基因编码了一种与化酶有很高相似性的蛋白质.
- 已经证明DnmZ是一种氨基糖尼特罗斯合成酶.
- DnmZ催化了提米丁-5'-二酸盐-l-epi-vancosamine的初始转化到一个环开放的产品.
- 这种反应通过以前未被描述的逆氧胺-阿尔多尔机制进行.
结论:
- DnmZ是独特的宝米辛糖分的生物合成中的关键酶.
- 由DnmZ催化的逆氧化-阿尔多尔反应代表了一种新的生物化学转化.
- 了解这种途径,可以了解复杂的甘化天然产品的生物合成.
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