The Use of In Silico Genome-Scale Models for the Rational Design of Minimal Cells

  title={The Use of In Silico Genome-Scale Models for the Rational Design of Minimal Cells},
  author={Jean-Christophe Lachance and S{\'e}bastien Rodrigue and Bernhard O. Palsson},
Organism-specific genome-scale metabolic models (GEMs) can be reconstructed using genome annotation and biochemical data available in literature. The systematic inclusion of biochemical reactions into a coherent metabolic network combined with the formulation of appropriate constraints reveals the set of metabolic capabilities harbored by an organism, hereby allowing the computation of growth phenotypes from genotype information. GEMs have been used thoroughly to assess growth capabilities… Expand
1 Citations
The relevance of enzyme specificity for coenzymes and the presence of 6-phosphogluconate dehydrogenase for polyhydroxyalkanoates production in the metabolism of Pseudomonas sp. LFM046.
The results indicate that the adjustment in cyclic Entner-Doudoroff pathway may be an interesting strategy for Pseudomonas putida and other bacteria to simultaneously meet divergent cell needs during cultivation phases of growth and PHA production. Expand


Predicting gene essentiality using genome-scale in silico models.
This chapter introduces the constraint-based modeling approach and focuses on its application to computationally predicting gene essentiality. Expand
Reconstructing genome-scale metabolic models with merlin
The merlin tool is a user-friendly Java application that aids the reconstruction of genome-scale metabolic models for any organism that has its genome sequenced, and expedites the transition from genomic data to draft metabolic models reconstructions exported in the SBML standard format. Expand
In silico method for modelling metabolism and gene product expression at genome scale.
The method presents a framework for investigating molecular biology and cellular physiology in silico and may allow quantitative interpretation of multi-omics data sets in the context of an integrated biochemical description of an organism. Expand
Genome-scale models of metabolism and gene expression extend and refine growth phenotype prediction
An ME‐Model for Escherichia coli is constructed—a genome‐scale model that seamlessly integrates metabolic and gene product expression pathways and formalizes the principle of growth optimization to enable the accurate prediction of multi‐scale phenotypes. Expand
COBRAme: A computational framework for genome-scale models of metabolism and gene expression
COBRAme provides tools to simplify constructing and editing ME-models to enable ME-model reconstructions for new organisms and is used to reconstruct a condensed E. coli ME- model called iJL1678b-ME. Expand
Improving the iMM904 S. cerevisiae metabolic model using essentiality and synthetic lethality data
This study provides a roadmap for the computationally driven correction of multi-compartment genome-scale metabolic models and demonstrates the value of synthetic lethals as curation agents. Expand
Integration of Biomass Formulations of Genome-Scale Metabolic Models with Experimental Data Reveals Universally Essential Cofactors in Prokaryotes
This work integrates biomass compositions from 71 manually curated genome-scale models, 33 large-scale gene essentiality datasets, enzyme-cofactor association data and a vast array of publications, revealing universally essential cofactors for prokaryotic metabolism and also others that are specific for phylogenetic branches or metabolic modes. Expand
A Genome-Scale Metabolic Reconstruction of Mycoplasma genitalium, iPS189
A systematic approach is introduced for the construction and curation of a genome-scale in silico metabolic model for M. genitalium and the approaches and tools described herein provide a roadmap for the automated construction of insilico metabolic models of other organisms. Expand
Essential metabolism for a minimal cell
The model, its comparison to in vivo essentiality and proteomics data yield specific hypotheses on gene functions and metabolic capabilities; and suggestions for several further gene removals guide future investigations of the minimal cell. Expand
The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities.
  • J. Edwards, B. Palsson
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2000
It was shown that based on stoichiometric and capacity constraints the in silico analysis was able to qualitatively predict the growth potential of mutant strains in 86% of the cases examined. Expand