Theoretical Improvements in Enzyme Efficiency Associated with Noisy Rate Constants and Increased Dissipation

Abstract

Previous studies have revealed the extraordinarily large catalytic efficiency of some enzymes. High catalytic proficiency is an essential accomplishment of biological evolution. Natural selection led to the increased turnover number, kcat, and enzyme efficiency, kcat/KM, of uni–uni enzymes, which convert a single substrate into a single product. We added or multiplied random noise with chosen rate constants to explore the correlation between dissipation and catalytic efficiency for ten enzymes: beta-galactosidase, glucose isomerase, β-lactamases from three bacterial strains, ketosteroid isomerase, triosephosphate isomerase, and carbonic anhydrase I, II, and T200H. Our results highlight the role of biological evolution in accelerating thermodynamic evolution. The catalytic performance of these enzymes is proportional to overall entropy production—the main parameter from irreversible thermodynamics. That parameter is also proportional to the evolutionary distance of β-lactamases PC1, RTEM, and Lac-1 when natural or artificial evolution produces the optimal or maximal possible catalytic efficiency. De novo enzyme design and attempts to speed up the rate-limiting catalytic steps may profit from the described connection between kinetics and thermodynamics.