在托邦类生物合成中的碳骨重组
Gregory M Sandala1, David M Smith, Leo Radom
1School of Chemistry and ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, University of Sydney, Sydney, NSW 2006, Australia. sandala@chem.usyd.edu.au
Journal of the American Chemical Society
|July 17, 2008
概括
量子化学计算揭示了用于类类生物合成的低能碳化通路. 这种协同的重排机制是将利托林转化为低胺的可行途径.
科学领域:
- 计算化学的计算化学
- 生物化学 生物化学
- 有机化学 有机化学
背景情况:
- 热带类化合物,如利托林和基胺,是重要的自然产物.
- 了解它们的生物合成途径对于药物化学和药物发现至关重要.
- 碳骨从利托林重新排列到基胺是一个关键的生物合成步骤.
研究的目的:
- 通过高层次量子化学计算,研究了利托林到基胺碳骨架重组的机制.
- 为了比较基于激素和碳酸的途径的能量需求,包括分阶段和协调机制.
- 探索酶相互作用如何影响这些重排障碍.
主要方法:
- 使用高级量子化学计算来建模反应路径.
- 研究了两个主要机制:分阶段 (碎片-重组) 和协调.
- 分析了基和碳酸中间体,以及部分质子化/脱质子化的影响.
主要成果:
- 基于碳酸的协同通路显示出明显较低的重排障碍 (47.4 kJ mol(-1)) 与基于基因的协同 (135.6 kJ mol(-1)) 和碎片化通路相比.
- 基质衍生基的氧化到碳酸被预测是容易的.
- 酶调制,通过部分质子化/脱质子化,可以进一步降低重新排列障碍,有利于碳酸的路径.
结论:
- 涉及碳酸的协同重新排列机制为托邦类生物合成中的碳骨架重新排列提供了一个可行的低能耗途径.
- 这种碳化途径在能量方面比基于基因的机制或碎片-重组路径更有利.
- 酶催化剂可能在优化这种途径中发挥作用,以便有效地将利托林转化为低胺.
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