Essential metabolism for a minimal cell

eLife

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[1] Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States;Department of Microbiology and Cell Science, University of Florida, Gainesville, United States;Department of Pharmacology and School of Pharmacy, University of California at San Diego, La Jolla, United States;Horticultural Sciences Department, University of Florida, Gainesville, United States;J Craig Venter Institute, La Jolla, United States;

关键词: JCVI-syn3A;    metabolic reconstruction;    transposon mutagenesis;    mycoplasma;    proteomics;    gene essentiality;    Other;   

DOI  :  10.7554/eLife.36842

来源: publisher

【 摘 要 】

10.7554/eLife.36842.001JCVI-syn3A, a robust minimal cell with a 543 kbp genome and 493 genes, provides a versatile platform to study the basics of life. Using the vast amount of experimental information available on its precursor, Mycoplasma mycoides capri, we assembled a near-complete metabolic network with 98% of enzymatic reactions supported by annotation or experiment. The model agrees well with genome-scale in vivo transposon mutagenesis experiments, showing a Matthews correlation coefficient of 0.59. The genes in the reconstruction have a high in vivo essentiality or quasi-essentiality of 92% (68% essential), compared to 79% in silico essentiality. This coherent model of the minimal metabolism in JCVI-syn3A at the same time also points toward specific open questions regarding the minimal genome of JCVI-syn3A, whicSynthetic Mycoplasma mycoides JCVI-syn1.0 clone sMmYCp235-1, complete sequenceh still contains many genes of generic or completely unclear function. In particular, the model, its comparison to in vivo essentiality and proteomics data yield specific hypotheses on gene functions and metabolic capabilities; and provide suggestions for several further gene removals. In this way, the model and its accompanying data guide future investigations of the minimal cell. Finally, the identification of 30 essential genes with unclear function will motivate the search for new biological mechanisms beyond metabolism.

【 授权许可】

CC BY