Work

Protein-constrained models pinpoints the role of underground metabolism in robustness of metabolic phenotypes

Year: 2025

Type: article

Abstract: Integrating enzyme parameters into constraint-based models have significantly improved the prediction of physiological and molecular traits. To further improve these models, we integrated promiscuous enzyme activities that jointly comprise the so-called underground metabolism by developing the CORAL toolbox, which increases the resolution of modeled enzyme resource allocation. Applying CORAL to a protein-constrained model of Escherichia coli revealed that underground metabolism resulted in larger flexibility of metabolic fluxes and enzyme usage. Simulating metabolic defects where the main activity of a promiscuous enzyme was blocked but promiscuous activities remained functional showed a small enzyme redistribution to the side activities. Further, blocking pairs of main activities showed that non-promiscuous enzymes exhibited larger impact on growth than promiscuous enzymes. These simulations showed that promiscuous enzymes can compensate for these defects, in line with experimental evidence. Together, our results indicated that promiscuous enzyme activities are vital to maintain robust metabolic function and growth.

Source: iScience

DOI: 10.1016/j.isci.2025.112126

Authors: Maurício Alexander de Moura Ferreira, Eduardo Luís Menezes de Almeida, Wendel Batista da Silveira, Zoran Nikoloski

Institutions: Universidade Federal de Viçosa, University of Potsdam, Max Planck Institute of Molecular Plant Physiology

Language: English

Topic: Microbial Metabolic Engineering and Bioproduction

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,240

Funder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior