It has been observed among natural RuBisCOs that an increased ability to distinguish between CO and O (larger values of S) corresponds with a decreased rate of carboxylation (lower values of V and K). The variation and trade-off between S and K has been observed across all photosynthetic organisms, from photosynthetic bacteria and algae to higher plants. Organisms using RuBisCOs with high values of V / K, and low values of S have localized RuBisCO to areas within the cell with artificially high local CO concentrations. In cyanobacteria, concentrations of CO are increased using a carboxysome, an icosahedral protein compartment about 100 nm in diameter that selectively uptakes bicarbonate and converts it to CO in the presence of RuBisCO. Organisms without a CCM, like certain plants, instead utilize RuBisCOs with high values of S and low values of V and K. It has been theorized that groups with a CCM have been able to maximize K at the expense of decreasing S, because artificially enhancing the concentration of CO would decrease the concentration of O and remove the need for high CO specificity. However, the opposite is true for organisms without a CCM, who must optimize S at the expense of K because O is readily present in the atmosphere.
This trade-off between S and V or K observed in extant organisms suggest that RuBisCO has evolved through geologic time to be maximally optimized in its current, modern environment. RuBisCO evolved over 2.5 billion years ago when atmospheric CO concentrations were 300 to 600 times higher than present day concentrations, and oxygen concentrations were only 5-18% of present-day levels. Therefore, because CO was abundant and O rare, there was no need for the ancestral RuBisCO enzyme to have high specificity. This is supported by the biochemical characterization of an ancestral RuBisCO enzyme, which has intermediate values of V and S between the extreme end-members.
It has been theorized that this ecological trade-off is due to the form that 2-carboxy-3-keto-D-arabinitol 1,5-bisphophate in its transient transition state before cleaving into two 3PGA molecules. The more closely the Mg-bound CO moiety resembles the carboxylate group in 2-carboxy-3-keto-D-arabinitol 1,5-bisphophate, the greater the structural difference between the transition states of carboxylation and oxygenation. The larger structural difference allows RuBisCO to better distinguish between CO and O, resulting in larger values of S. However, this increasing structural similarity between the transition state and the product state requires strong binding at the carboxyketone group, and this binding is so strong that the rate of cleavage into two product 3PGA molecules is slowed. Therefore, an increased specificity for CO over O necessitates a lower overall rate of carboxylation. This theory implies that there is a physical chemistry limitation at the heart of Rubisco's active site, and may preclude any efforts to engineer a simultaneously more selective and faster Rubisco.