An approach to learn regulation to maximize growth and entropy production rates in metabolism

Autor: Ethan King, Jesse Holzer, Justin A. North, William R. Cannon
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Systems Biology, Vol 3 (2023)
Druh dokumentu: article
ISSN: 2674-0702
DOI: 10.3389/fsysb.2023.981866
Popis: Elucidating cell regulation remains a challenging task due to the complexity of metabolism and the difficulty of experimental measurements. Here we present a method for prediction of cell regulation to maximize cell growth rate while maintaining the solvent capacity of the cell. Prediction is formulated as an optimization problem using a thermodynamic framework that can leverage experimental data. We develop a formulation and variable initialization procedure that allows for computing solutions of the optimization with an interior point method. The approach is applied to photoheterotrophic growth of Rhodospirilium rubrum using ethanol as a carbon source, which has applications to biosynthesis of ethylene production. Growth is captured as the rate of synthesis of amino acids into proteins, and synthesis of nucleotide triphoshaptes into RNA and DNA. The method predicts regulation that produces a high rate of protein and RNA synthesis while DNA synthesis is reduced close to zero in agreement with production of DNA being turned off for much of the cell cycle.
Databáze: Directory of Open Access Journals