PT - JOURNAL ARTICLE AU - Avi Flamholz AU - Noam Prywes AU - Uri Moran AU - Dan Davidi AU - Yinon Bar-On AU - Luke Oltrogge AU - David Savage AU - Ron Milo TI - Revisiting tradeoffs in Rubisco kinetic parameters AID - 10.1101/470021 DP - 2018 Jan 01 TA - bioRxiv PG - 470021 4099 - http://biorxiv.org/content/early/2018/11/14/470021.short 4100 - http://biorxiv.org/content/early/2018/11/14/470021.full AB - Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase (Rubisco) is not only the dominant enzyme in the biosphere, responsible for the vast majority of carbon fixation, but also one of the best characterized enzymes. Enhanced Rubisco catalysis is expected to increase crop yields, but a substantially improved enzyme has evaded bioengineers for decades. Based on correlations between Rubisco’s kinetic parameters, it is widely posited that tradeoffs stemming from the catalytic mechanism strictly constrain Rubisco’s maximum catalytic potential. Though compelling, the reasoning that established that view was based on data from only ≈20 organisms. Here we re-examine these tradeoffs with an expanded dataset including data from >200 organisms. We find that most correlations are substantially attenuated, with the inverse relationship between carboxylation kcat and specificity SC/O being a key example. However, the correlation predicted by one tradeoff model is stronger and more significant in our expanded dataset. In this model, increased catalytic efficiency (kcat/KM) for carboxylation requires a similar increase in catalytic efficiency for the competing oxygenation reaction, evidenced here by a strong power-law correlation between those catalytic efficiencies. In contrast to previous work, our results imply that Rubisco evolution is constrained mostly by the physicochemical limits of O2/CO2 recognition, which should reframe efforts to understand and engineer this very central enzyme.Significance All plants, algae and cyanobacteria rely on the Calvin-Benson-Bassham (CBB) cycle for growth. Rubisco is the central enzyme of the CBB cycle and the most abundant enzyme on Earth. While it is often claimed that Rubisco is slow, its catalytic rate is just below the average enzyme. Yet it is surprising that Rubisco is not faster given its centrality and abundance. Previous analyses of Rubisco kinetic parameters raised doubts that the enzyme can be improved. Here we examine a new compendium of Rubisco kinetic parameters for evidence of proposed constraints on Rubisco catalysis. Only one proposal is strongly supported by the data, which argues for re-evaluation of our understanding of one of the most impactful proteins in Earth’s history.