RT Journal Article
SR Electronic
T1 Universal Design Principle to Enhance Enzymatic Activity using the Substrate Affinity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.02.01.526728
DO 10.1101/2023.02.01.526728
A1 Hideshi Ooka
A1 Yoko Chiba
A1 Ryuhei Nakamura
YR 2023
UL http://biorxiv.org/content/early/2023/02/03/2023.02.01.526728.abstract
AB Design principles to improve enzymatic activity are essential to promote energy-material conversion using biological systems. For more than a century, the Michaelis-Menten equation has provided a fundamental framework of enzymatic activity. However, there is still no concrete guideline on how the parameters should be optimized to enhance enzymatic activity. Here, we demonstrate that tuning the Michaelis-Menten constant (Km) to the substrate concentration (S) maximizes enzymatic activity. This guideline (Km = S) was obtained by applying the Brønsted (Bell)-Evans-Polanyi (BEP) principle of heterogeneous catalysis to the Michaelis-Menten equation, and is robust even with mechanistic deviations such as reverse reactions and inhibition. Furthermore, Km and S are consistent to within an order of magnitude over an experimental dataset of approximately 1000 wild-type enzymes, suggesting that even natural selection follows this principle. The concept of an optimum Km offers the first quantitative guideline towards improving enzymatic activity which can be used for highthroughput enzyme screening.Competing Interest StatementThe authors have declared no competing interest.