Nature | Optimal enzyme utilization suggests that concentrations and thermodynamics determine binding mechanisms and enzyme saturations

Sahin, A., Weilandt, D.R. & Hatzimanikatis, V. Optimal enzyme utilization suggests that concentrations and thermodynamics determine binding mechanisms and enzyme saturations. Nat Commun 14, 2618 (2023). https://doi.org/10.1038/s41467-023-38159-4        

Summary by: Aakash Khurana

The paper was published investigates how enzymes achieve optimal performance. It focuses on how factors like substrate concentration and the inherent energetics of the reaction influence the way enzymes bind to substrates (binding mechanism) and how much substrate they bind at a time (saturation) for maximum efficiency.

Main Idea: Enzymes operate under evolutionary pressure to maximize their catalytic efficiency. This research explores how factors like concentration and thermodynamics influence an enzyme's mechanism of action (binding order) and the level of substrate saturation for optimal performance.

Key Points:

• The researchers developed a new method to analyze the distribution of energy forces and various enzyme states during operation.
• This method was applied to understand the Michaelis-Menten mechanism (common single-substrate enzyme reaction) and random-ordered multi-substrate mechanisms.
• Their findings suggest that under physiological conditions (typical cell environment), a random binding mechanism is generally more favorable for enzymes compared to ordered mechanisms.
• The study also revealed that the optimal level of enzyme saturation (how much substrate is bound to the enzyme) depends on the concentrations of reactants (substrate and product) within the system. At low reactant concentrations, the enzyme should operate with low saturation. As reactant concentrations increase, the optimal saturation level also increases, but this rise slows down significantly at higher concentrations.
• Interestingly, these findings seem independent of the thermodynamic displacement of the reaction (how far the reaction is from equilibrium).

Implications:

• This research can guide the process of directed evolution, which aims to modify enzymes for specific purposes.
• The findings can aid in identifying the limitations of directly evolving enzymes.
• The framework provides a tool to gain deeper insights into enzyme kinetics.

Overall Significance:

This research provides a new framework to analyze optimal enzyme function. It suggests that the environment an enzyme operates in plays a crucial role in determining its binding mechanism and saturation levels for peak performance. This knowledge can be valuable for:

• Understanding cellular metabolism: By explaining how enzymes adapt their behavior, this framework sheds light on how cells respond to genetic and environmental changes.
• Directed enzyme evolution: This method could guide efforts to engineer enzymes with desired properties.
• Identifying limitations of enzyme evolution: The framework might help determine the maximum efficiency achievable through natural selection.

Note: Please note that this summary does not include all of the research article's information. If you find the summary interesting, please read the research paper that is linked below.