A genome-scale metabolic reconstruction of Mycoplasma genitalium, iPS189

With a genome size of approximately 580 kb and approximately 480 protein coding regions, Mycoplasma genitalium is one of the smallest known self-replicating organisms and, additionally, has extremely fastidious nutrient requirements. The reduced genomic content of M. genitalium has led researchers t...

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Bibliographic Details
Published in:PLoS computational biology 2009-02, Vol.5 (2), p.e1000285-e1000285
Main Authors: Suthers, Patrick F, Dasika, Madhukar S, Kumar, Vinay Satish, Denisov, Gennady, Glass, John I, Maranas, Costas D
Format: Article
Language:English
Subjects:
Automation
Biomass
Computational Biology/Metabolic Networks
Computational Biology/Systems Biology
Genes, Essential
Genetics and Genomics/Bioinformatics
Genome, Bacterial
Genomes
Genomics
Metabolites
Metabolome - genetics
Metabolomics - methods
Models, Biological
Mycoplasma genitalium - genetics
Mycoplasma genitalium - metabolism
Nutrigenomics
Organisms
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Summary:With a genome size of approximately 580 kb and approximately 480 protein coding regions, Mycoplasma genitalium is one of the smallest known self-replicating organisms and, additionally, has extremely fastidious nutrient requirements. The reduced genomic content of M. genitalium has led researchers to suggest that the molecular assembly contained in this organism may be a close approximation to the minimal set of genes required for bacterial growth. Here, we introduce a systematic approach for the construction and curation of a genome-scale in silico metabolic model for M. genitalium. Key challenges included estimation of biomass composition, handling of enzymes with broad specificities, and the lack of a defined medium. Computational tools were subsequently employed to identify and resolve connectivity gaps in the model as well as growth prediction inconsistencies with gene essentiality experimental data. The curated model, M. genitalium iPS189 (262 reactions, 274 metabolites), is 87% accurate in recapitulating in vivo gene essentiality results for M. genitalium. Approaches and tools described herein provide a roadmap for the automated construction of in silico metabolic models of other organisms.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1000285