Fundamental Bioengineering

6Genome-Scale Models

Basti Bergdahl, Nikolaus Sonnenschein, Daniel Machado, Markus Herrgård and Jochen Förster

Summary

An introduction to genome-scale models, how to build and use them, will be given in this chapter. Genome-scale models have become an important part of systems biology and metabolic engineering, and are increasingly used in research, both in academica and in industry, both for modeling chemical production and for fundamental studies aiming at describing and explaining phenotypic behavior of microbial and mammalian cells.

6.1 Introduction

Chapter 4 introduced the concept of metabolic flux analysis, a powerful tool for modeling metabolic behavior and estimating intracellular and extracellular fluxes. In metabolic flux analysis, reduced or lumped models of the central carbon metabolism, or parts of metabolism, such as glycolysis, are applied, the metabolic behavior is described, and intracellular fluxes are simulated. The models are supplemented with experimental data such as production rates and sugar consumption rates. Chapter 6 is a primer on genome-scale models. It gives an introduction to building metabolic reconstructions and shows examples of the application of genome-scale models, that is, for chemical production or drug compound identification. Genome-scale models became available shortly after the complete genomes were sequenced, and today with the availability of next-generation sequencing methods that allow overnight sequencing of complete microbial ...