In-Depth Computational Analysis of Natural and Artificial Carbon Fixation Pathways

In the recent years, engineering new-to-nature CO 2 - and C1-fixing metabolic pathways made a leap forward. New, artificial promise higher yields activity than natural ones like Calvin-Benson-Bassham (CBB) cycle. The question remains how to best predict their in vivo performance what actually makes one pathway “better” another. this context, we explore aerobic carbon fixation by computational approach compare them based on specific yield methanol, formate, /H considering kinetics thermodynamics of reactions. Besides found nature or implemented laboratory, included two completely new cycles with favorable features: reductive citramalyl-CoA cycle 2-hydroxyglutarate-reverse tricarboxylic acid A comprehensive kinetic data set was collected for all enzymes pathways, missing were sampled Parameter Balancing algorithm. Kinetic thermodynamic fed Enzyme Cost Minimization algorithm check respective inconsistencies calculate pathway-specific activities. activities glycine pathway, CETCH cycle, predicted match superior product-substrate yield. However, CBB performed better terms compared alternative previously thought. We make an argument that stoichiometric is likely not most important design criterion Still, paretooptimal simulations C1 substrates therefore hold great potential future applications Industrial Biotechnology Synthetic Biology.