In the recent years, engineering new-to-nature CO2 and C1 fixing metabolic pathways made a leap forward. These new, artificial pathways promise higher yields and activity than natural ones like the Calvin-Benson-Bassham cycle. The question remains how to best predict their in vivo performance and what actually makes one pathway "better" than another. In this context, we explore aerobic carbon fixation pathways by a computational approach and compare them based on their ATP-efficiency and specific activity considering the kinetics and thermodynamics of the reactions. Beside natural pathways, this included the artificial Reductive Glycine Pathway, the CETCH cycle and two completely new cycles with superior stoichiometry: The Reductive Citramalyl-CoA cycle and the 2-Hydroxyglutarate-Reverse Tricarboxylic Acid cycle. A comprehensive kinetic data set was collected for all enzymes of all pathways and missing kinetic data was sampled with the Parameter Balancing algorithm. Kinetic and thermodynamic data were fed to the Enzyme Cost Minimization algorithm to check for respective inconsistencies and calculate pathway specific activities. We found that the Reductive Glycine Pathway, the CETCH cycle and the new Reductive Citramalyl-CoA cycle were predicted to have higher ATP-efficiencies and specific activities than the natural cycles. The Calvin Cycle performed better than previously thought, however. It can be concluded that the weaker overall characteristics in the design of the Calvin Cycle might be compensated by other benefits like robustness, low nutrient demand and a good compatibility with the host's physiological requirements. Nevertheless, the artificial carbon fixation cycles hold great potential for future applications in Industrial Biotechnology and Synthetic Biology.

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天然和人造碳固定路径的深入计算分析

近年来，设计新的自然界中的CO2和C1固定代谢途径取得了飞跃。这些新的人工途径比诸如Calvin-Benson-Bassham循环等自然途径具有更高的产量和活性。问题仍然是如何最好地预测它们的体内性能，以及究竟是什么使一种途径比另一种途径“更好”。在这种情况下，我们通过一种计算方法探索了好氧碳固定途径，并根据它们的ATP效率和比活性（考虑了反应的动力学和热力学）对它们进行了比较。除天然途径外，这还包括人工还原甘氨酸途径，CETCH循环和两个化学计量优异的全新循环：还原柠檬酸辅酶A循环和2-羟基戊二酸酯-反向三羧酸循环。收集了所有途径的所有酶的综合动力学数据集，并使用参数平衡算法对缺失的动力学数据进行了采样。动力学和热力学数据被输入到酶成本最小化算法中，以检查各自的不一致之处并计算途径特异性活性。我们发现，还原性甘氨酸途径，CETCH循环和新的还原性Citramalyl-CoA循环预计比自然循环具有更高的ATP效率和比活性。但是，卡尔文循环的表现要好于先前的想象。可以得出结论，加尔文循环设计中较弱的总体特征可能会被其他好处所补偿，例如健壮性，低养分需求以及与宿主生理需求的良好相容性。不过，