PT  - JOURNAL ARTICLE
AU  - Hideshi Ooka
AU  - Yoko Chiba
AU  - Ryuhei Nakamura
TI  - Universal Design Principle to Enhance Enzymatic Activity using the Substrate Affinity
AID  - 10.1101/2023.02.01.526728
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.02.01.526728
4099  - http://biorxiv.org/content/early/2023/02/03/2023.02.01.526728.short
4100  - http://biorxiv.org/content/early/2023/02/03/2023.02.01.526728.full
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.