a genome-scale metabolic reconstruction of mycoplasma genitalium, ips189一个公司代谢尿道支原体的重建,ips189.pdfVIP

A Genome-Scale Metabolic Reconstruction of Mycoplasma genitalium, i PS189 1 1 2 3 3 Patrick F. Suthers , Madhukar S. Dasika , Vinay Satish Kumar , Gennady Denisov , John I. Glass , Costas D. Maranas1* 1 Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, United States of America, 2 Department of Industrial Engineering, The Pennsylvania State University, University Park, Pennsylvania, United States of America, 3 J. Craig Venter Institute, Rockville, Maryland, United States of America Abstract With a genome size of ,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