Rubisco is not really so bad

Ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco) is the most widespread carboxylating enzyme in autotrophic organisms. Its kinetic and structural properties have been intensively studied for more than half a century. Yet important aspects of the catalytic mechanism remain poorly understood, especially the oxygenase reaction. Because of its relatively modest turnover rate (a few catalytic events per second) and the competitive inhibition by oxygen, Rubisco is often viewed as an inefficient catalyst for CO2 fixation. Considerable efforts have been devoted to improving its catalytic efficiency, so far without success. In this review, we re‐examine Rubisco's catalytic performance by comparison with other chemically related enzymes. We find that Rubisco is not especially slow. Furthermore, considering both the nature and the complexity of the chemical reaction, its kinetic properties are unremarkable. Although not unique to Rubisco, oxygenation is not systematically observed in enolate and enamine forming enzymes and cannot be considered as an inevitable consequence of the mechanism. It is more likely the result of a compromise between chemical and metabolic imperatives. We argue that a better description of Rubisco mechanism is still required to better understand the link between CO2 and O2 reactivity and the rationale of Rubisco diversification and evolution. Rubisco, the most widespread carboxylase in photosynthetic organisms, is often considered to be slow and unable to properly distinguish between its CO2 substrate and O2, thereby limiting photosynthesis and growth in crops. In this review, we compare its catalytic performances with that of many other known enzymes and show that in this broader context Rubisco cannot be considered a particularly inefficient catalyst. We also build on the growing knowledge on chemically‐related enzymes to conclude that its oxygenase function cannot be considered mechanistically inevitable. We thus argue that more work is needed to unravel the link between CO2 and O2 reactivity, which is essential to understanding the evolution of the Rubisco family, and to guiding more efficiently engineering strategies in crops.