Essential metabolism for a minimal cell

Marian Breuer, Tyler M. Earnest, Chuck Merryman, Kim S. Wise, Lijie Sun, Michaela R. Lynott, Clyde A. Hutchison, Hamilton O. Smith, John D. Lapek, David J. Gonzalez, Valérie de Crécy-Lagard, Drago Haas, Andrew D. Hanson, Piyush Labhsetwar, John I. Glass, Zaida Luthey-Schulten

Research output: Contribution to journalArticle

Abstract

JCVI-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, which 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.

Original languageEnglish (US)
Article numbere36842
JournaleLife
Volume8
DOIs
StatePublished - Jan 18 2019

Keywords

  • JCVI-syn3A
  • computational biology
  • gene essentiality
  • metabolic reconstruction
  • mycoplasma
  • proteomics
  • systems biology
  • transposon mutagenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Breuer, M., Earnest, T. M., Merryman, C., Wise, K. S., Sun, L., Lynott, M. R., Hutchison, C. A., Smith, H. O., Lapek, J. D., Gonzalez, D. J., de Crécy-Lagard, V., Haas, D., Hanson, A. D., Labhsetwar, P., Glass, J. I., & Luthey-Schulten, Z. (2019). Essential metabolism for a minimal cell. eLife, 8, [e36842]. https://doi.org/10.7554/eLife.36842