Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

ECMpy, a Simplified Workflow for Constructing Enzymatic Constrained Metabolic Network Model

Version 1 : Received: 1 December 2021 / Approved: 3 December 2021 / Online: 3 December 2021 (10:20:49 CET)

A peer-reviewed article of this Preprint also exists.

Mao, Z.; Zhao, X.; Yang, X.; Zhang, P.; Du, J.; Yuan, Q.; Ma, H. ECMpy, a Simplified Workflow for Constructing Enzymatic Constrained Metabolic Network Model. Biomolecules 2022, 12, 65. Mao, Z.; Zhao, X.; Yang, X.; Zhang, P.; Du, J.; Yuan, Q.; Ma, H. ECMpy, a Simplified Workflow for Constructing Enzymatic Constrained Metabolic Network Model. Biomolecules 2022, 12, 65.

Journal reference: Biomolecules 2022, 12, 65
DOI: 10.3390/biom12010065

Abstract

Genome-scale metabolic models (GEMs) have been widely used for phenotypic prediction of microorganisms. However, the lack of other constraints in the stoichiometric model often leads to a large metabolic solution space inaccessible. Inspired by previous studies that take allocation of macromolecule resources into account, we developed a simplified Python-based workflow for constructing enzymatic constrained metabolic network model (ECMpy) and constructed an enzyme-constrained model for Escherichia coli (eciML1515) by directly adding a total enzyme amount constraint in the latest version of GEM for E. coli (iML1515), considering the protein subunit composition in the reaction, and automated calibration of enzyme kinetic parameters. Using eciML1515, we predicted the overflow metabolism of E. coli and revealed that redox balance was the key reason for the difference between E. coli and Saccharomyces cerevisiae in overflow metabolism. The growth rate predictions on 24 single-carbon sources were improved significantly when compared with other enzyme-constrained models of E. coli. Finally, we revealed the tradeoff between enzyme usage efficiency and biomass yield by exploring the metabolic behaviors under different substrate consumption rates. Enzyme-constrained models can improve simulation accuracy and thus can predict cellular phenotypes under various genetic perturbations more precisely, providing reliable guidance for metabolic engineering.

Keywords

Enzyme-constrained model; Escherichia coli; Enzyme kinetics; Protein subunit; Overflow metabolism

Subject

BIOLOGY, Physiology

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