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

Asli Sahin, Daniel R. Weilandt and Vassily Hatzimanikatis ()
Additional contact information
Asli Sahin: Ecole Polytechnique Federale de Lausanne (EPFL)
Daniel R. Weilandt: Ecole Polytechnique Federale de Lausanne (EPFL)
Vassily Hatzimanikatis: Ecole Polytechnique Federale de Lausanne (EPFL)

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Deciphering the metabolic functions of organisms requires understanding the dynamic responses of living cells upon genetic and environmental perturbations, which in turn can be inferred from enzymatic activity. In this work, we investigate the optimal modes of operation for enzymes in terms of the evolutionary pressure driving them toward increased catalytic efficiency. We develop a framework using a mixed-integer formulation to assess the distribution of thermodynamic forces and enzyme states, providing detailed insights into the enzymatic mode of operation. We use this framework to explore Michaelis-Menten and random-ordered multi-substrate mechanisms. We show that optimal enzyme utilization is achieved by unique or alternative operating modes dependent on reactant concentrations. We find that in a bimolecular enzyme reaction, the random mechanism is optimal over any other ordered mechanism under physiological conditions. Our framework can investigate the optimal catalytic properties of complex enzyme mechanisms. It can further guide the directed evolution of enzymes and fill in the knowledge gaps in enzyme kinetics.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38159-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38159-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38159-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().