Accomplishments in genome‐scale in silico modeling for industrial and medical biotechnology

Abstract

Driven by advancements in high-throughput biological technologies and the growing number of sequenced genomes, the construction of in silico models at the genome scale has provided powerful tools to investigate a vast array of biological systems and applications. Here, we review comprehensively the uses of such models in industrial and medical biotechnology, including biofuel generation, food production, and drug development. While the use of in silico models is still in its early stages for delivering to industry, significant initial successes have been achieved. For the cases presented here, genome-scale models predict engineering strategies to enhance properties of interest in an organism or to inhibit harmful mechanisms of pathogens or in disease. Going forward, genome-scale in silico models promise to extend their application and analysis scope to become a transformative tool in biotechnology. As such, genome-scale models can provide a basis for rational genome-scale engineering and synthetic biology.

Genome-Scale Metabolic Reconstruction and Hypothesis Testing in the Methanogenic Archaeon Methanosarcina acetivorans C2A

“…Automation is needed to continue the exponential increase in the number of genome-scale metabolic models (43,45). However, automated reconstructions for methanogens are still particularly problematic for three major reasons: (i) automated predictions tend to be overly homogenized due to their strong reliance on homologybased methods; (ii) reaction and gene databases have more limited coverage of the Archaea than of the other domains of life; and (iii) the energy conservation mechanisms of methanogens are highly specialized (14).…”

Biotechnological and bioinformatics approaches for augmentation of biohydrogen production: A review

“…Initially the metabolic network of C. reinhardtii generated from literature sources and functional annotation lead to the identification of genes in need of experimental definition and validation that finally refines the model through verification of hypothetical transcript existence. As a result alternative enzymes were integrated to fill the pathway gaps, providing the basis for metabolic engineering towards improved biofuel production [15,82]. Similarly, in silico metabolic models and metabolic flux analysis study for increased H 2 production are available for several H 2 producers [92,[109][110][111][112][113].…”

“…An accurate genome-scale model of an organism help us in studying the effect of genetic and environmental perturbations on it, and hence this information actuate experiments in the area of metabolic engineering [15]. Ever since the development of the first genome scale model in Haemophilus influenzae [16], the available high-throughput biological data have been utilized efficiently for systems level modeling approaches [15]. The modeling and construction of biological components, functions and organisms non existing in nature or redesigning existing biological systems to perform new functions is considered as Synthetic biology [17].…”

Predicting network functions with nested patterns

“…Briefly, GSMs represent the reaction structures of biochemical conversions of compounds (metabolites) along with constraints on these conversions such as those implied by directed reactions. GSMs are widely used to predict condition-dependent growth and metabolism, or to engineer metabolic pathways for various organisms 15,16 . However, reconstructing high-quality GSMs still requires extensive expert knowledge 17 because of erroneous and contradicting database entries 18,19 , unknown metabolites or reactions 20 and thermodynamically infeasible or unconstrained reactions 21 .…”