Essential metabolism for a minimal cell
- University of Illinois at Urbana-Champaign, United States
- J Craig Venter Institute, United States
- University of California, San Diego, United States
- University of Florida, United States
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.
Data availability
Proteomics: data were uploaded to MassIVE (massive.ucsd.edu) with dataset identifier MSV000081687 and ProteomeXchange with dataset identifier PXD008159. All other new data are included in the manuscript and supporting files.
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Proteomic analysis of JCVI-Syn3A.MassIVE, MSV000081687.
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Synthetic bacterium JCVI-Syn3.0 strain 6d, complete genomeNCBI Nucleotide, CP016816.2.
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Synthetic bacterium JCVI-Syn3.0, complete genomeNCBI Nucleotide, CP014940.1.
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Mycoplasma pneumoniae M129, complete genomeNCBI Nucleotide, U00089.2.
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Escherichia coli B str. REL606, complete genomeNCBI Nucleotide, NC_012967.1.
Article and author information
Author details
Zaida Luthey-Schulten
Funding
National Science Foundation (PHY 1430124 Postdoctoral Fellowship)
- Marian Breuer
National Institutes of Health (K12 GM06852)
- John D Lapek
University of California (Office of the President)
- David J Gonzalez
Ray Thomas Edwards Foundation
- David J Gonzalez
J Craig Venter Institute
- Chuck Merryman
- Kim S Wise
- Clyde A Hutchison
- Hamilton O Smith
- John I Glass
National Science Foundation (PHY 1430124)
- Marian Breuer
- Tyler M Earnest
- Zaida Luthey-Schulten
National Science Foundation (MCB-1611711)
- Valérie de Crécy-Lagard
- Andrew D Hanson
National Science Foundation (MCB-1244570)
- Marian Breuer
- Tyler M Earnest
- Zaida Luthey-Schulten
Department of Energy (ORNL 4000134575)
- Piyush Labhsetwar
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Breuer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Essential metabolism for a minimal cell
eLife 8:e36842.
https://doi.org/10.7554/eLife.36842
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