Computational protein design enables a novel one-carbon assimilation pathway
Computational protein design enables a novel one-carbon assimilation pathway
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DOI：
10.1073/pnas.1500545112
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发表时间：
2015-03-24
影响因子：
11.1
通讯作者：
Baker, David
中科院分区：
文献类型：
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作者：
Siegel, Justin B.;Smith, Amanda Lee;Baker, David
我们描述了一种计算设计的酶，甲醇酶(FLS)，它催化三个一碳的甲醛分子碳化成一个三碳的二羟基丙酮分子。FLS的存在使得设计一种新的固碳途径，即甲醇酶途径成为可能，该途径由少量热力学上有利的化学转化组成，在中央代谢中将甲酸盐转化为三碳糖。据预测，甲醛酶途径比任何自然发生的一碳同化途径更有效地利用碳，并具有更少的反向通量。当添加了执行该途径中其他步骤的酶时，FLS在体外将甲酸盐转化为二羟丙酮磷酸和其他中心代谢物。这些结果表明，现代蛋白质工程和设计工具可以促进构建一种全新的生物合成途径。
We describe a computationally designed enzyme, formolase (FLS), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence of FLS enables the design of a new carbon fixation pathway, the formolase pathway, consisting of a small number of thermodynamically favorable chemical transformations that convert formate into a three-carbon sugar in central metabolism. The formolase pathway is predicted to use carbon more efficiently and with less backward flux than any naturally occurring one-carbon assimilation pathway. When supplemented with enzymes carrying out the other steps in the pathway, FLS converts formate into dihydroxyacetone phosphate and other central metabolites in vitro. These results demonstrate how modern protein engineering and design tools can facilitate the construction of a completely new biosynthetic pathway.