Evolution of Enzymes, 'Tunneling' Through Instead of Going Over the Wall... Elucidating the Use of Quantum Tunneling in Artific

Abstract

• Analyzed the proton quantum tunneling mechanism targeting enzymes designed by directed evolution in the laboratory. • Confirmed that the evolutionary process strategically and selectively optimizes tunneling to overcome classical chemical barriers when they increase. • Presented an answer to a long-standing puzzle in enzymology through a combined study of kinetic isotope effect (KIE) measurements and molecular dynamics simulations. [Quantum Biology Society] Natural enzymes are powerful catalysts that accelerate reaction rates by up to 10¹⁵ times compared to the solution state by lowering the activation energy of chemical reactions. While quantum tunneling has been pointed out as the secret to this phenomenal speed, how the evolutionary process controls and utilizes this quantum phenomenon has finally been elucidated. Recently, a paper titled "Directed Evolution's Selective Use of Quantum Tunneling in Designed Enzymes—A Combined Theoretical and Experimental Study" was published in the prominent physical chemistry journal J Phys Chem B, drawing the attention of the academic community. This study was led by a joint research team including Professor Steven D. Schwartz of the University of Arizona and the University of Manchester in the UK. ■ Quantum Tunneling 'Passing Through' Instead of Going Over the Reaction Barrier One of the core questions in enzymology has been, "How much does the evolutionary process intervene with the quantum tunneling mechanism that passes through the barrier, instead of overcoming the chemical energy barrier?" To answer this question, the research team used Morita-Baylis-Hillman (MBH) reaction enzymes artificially designed through directed evolution techniques in a laboratory environment as a research model. They precisely analyzed the contribution of quantum mechanics in the carbon-hydrogen (C-H) bond cleavage process of the proton, which is the core of the reaction. ■ Quantum Mechanics Becomes a Weapon of Evolution... "Uses Tunneling When Disadvantaged" The research team combined the experimental method of measuring kinetic isotope effects (KIE) and the theoretical approach of transition path sampling (TPS)-based molecular dynamics simulations. The analysis results showed that the evolution of enzymes does not occur randomly. Surprisingly, the evolutionary process strategically and selectively optimizes proton quantum tunneling as a kind of secret weapon to overcome situations where the reaction becomes difficult because the classical chemical free energy barrier actually increases due to the optimization of other processes. In other words, enzymes do not simply evolve solely in the direction of lowering the chemical barrier; they actively utilize a detour that maximizes quantum mechanical probability as needed, allowing particles to pass through the barrier as if teleporting. ■ A New Paradigm in Artificial Enzyme Design This study is a groundbreaking achievement that demonstrates, through the perfect convergence of experiment and theory, how enzymes selectively utilize quantum effects during the evolutionary process to maximize their catalytic capabilities. By demonstrating the fact that living organisms use quantum mechanics as a tool to overcome the limits of classical physics, it is expected to present a new paradigm for high-efficiency artificial enzyme design and quantum biology-based new drug development in the future.