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一个半合成生物的进步

Vivian T Dien¹, Matthew Holcomb¹, Aaron W Feldman¹

¹Department of Chemistry , The Scripps Research Institute , La Jolla , California 92037 United States.

Journal of the American Chemical Society

|November 13, 2018

概括

新的非自然基对 (UBPs) 在半合成生物 (SSOs) 中表现出更好的保留. 这些由疏水力介导的UBP增强了非正规氨基酸的遗传信息存储和蛋白质生产.

科学领域:

合成生物学
分子生物学
生物化学

背景情况:

不自然的基因对 (UBP) 扩展了遗传信息存储的范围,超出了自然的DNA.
之前的UBPs,如dNaM-dTPT3,依赖于疏水相互作用,但在半合成生物 (SSO) 中面临保留挑战.

研究的目的:

开发和评估基于基的新型dNaM类似物 (dPTMO,dMTMO) 以改善SSO中的UBP保留和功能.
优化SSO性能以存储增加的遗传信息,并生产非正规氨基酸的蛋白质.

主要方法:

对dPTMO- dTPT3和dMTMO- dTPT3UBPs的合成和体外表征.
在SSO中对UBP保留和复制效率的体内评估.
模拟研究以阐明改善UBP保留的分子基础.
使用新型UBP进行RNA转录和蛋白质生成的评估.

主要成果:

在体外,dPTMO-dTPT3和dMTMO-dTPT3的性能与dNaM-dTPT3相当或略低.
在体内,dMTMO- dTPT3 特别是dPTMO- dTPT3 在SSO中显著保持较高.
在体内保留的改善归因于增强的复制,而不是核三酸盐进口.
建模表明,硫原子调解核间基相互作用,这对复制至关重要.
新型UBP有效地模拟RNA转录,并导致更有效地将非正规氨基酸纳入蛋白质.

结论:

dPTMO-dTPT3和dMTMO-dTPT3代表了SSO的重大进步,使信息存储和检索更有效.
在体内环境中评估合成生物学成分对于优化至关重要.
疏水和包装相互作用可以有效地取代DNA复制中的键.
这项工作为具有扩大遗传信息能力的SSO铺平了道路.

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