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Essential metabolism for a minimal cell.
Breuer, Marian; Earnest, Tyler M; Merryman, Chuck; Wise, Kim S; Sun, Lijie; Lynott, Michaela R; Hutchison, Clyde A; Smith, Hamilton O; Lapek, John D; Gonzalez, David J; de Crécy-Lagard, Valérie; Haas, Drago; Hanson, Andrew D; Labhsetwar, Piyush; Glass, John I; Luthey-Schulten, Zaida.
Afiliação
  • Breuer M; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States.
  • Earnest TM; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States.
  • Merryman C; J Craig Venter Institute, La Jolla, United States.
  • Wise KS; J Craig Venter Institute, La Jolla, United States.
  • Sun L; J Craig Venter Institute, La Jolla, United States.
  • Lynott MR; J Craig Venter Institute, La Jolla, United States.
  • Hutchison CA; J Craig Venter Institute, La Jolla, United States.
  • Smith HO; J Craig Venter Institute, La Jolla, United States.
  • Lapek JD; Department of Pharmacology and School of Pharmacy, University of California at San Diego, La Jolla, United States.
  • Gonzalez DJ; Department of Pharmacology and School of Pharmacy, University of California at San Diego, La Jolla, United States.
  • de Crécy-Lagard V; Department of Microbiology and Cell Science, University of Florida, Gainesville, United States.
  • Haas D; Department of Microbiology and Cell Science, University of Florida, Gainesville, United States.
  • Hanson AD; Horticultural Sciences Department, University of Florida, Gainesville, United States.
  • Labhsetwar P; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States.
  • Glass JI; J Craig Venter Institute, La Jolla, United States.
  • Luthey-Schulten Z; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States.
Elife ; 82019 01 18.
Article em En | MEDLINE | ID: mdl-30657448
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.
One way that researchers can test whether they understand a biological system is to see if they can accurately recreate it as a computer model. The more they learn about living things, the more the researchers can improve their models and the closer the models become to simulating the original. In this approach, it is best to start by trying to model a simple system. Biologists have previously succeeded in creating 'minimal bacterial cells'. These synthetic cells contain fewer genes than almost all other living things and they are believed to be among the simplest possible forms of life that can grow on their own. The minimal cells can produce all the chemicals that they need to survive ­ in other words, they have a metabolism. Accurately recreating one of these cells in a computer is a key first step towards simulating a complete living system. Breuer et al. have developed a computer model to simulate the network of the biochemical reactions going on inside a minimal cell with just 493 genes. By altering the parameters of their model and comparing the results to experimental data, Breuer et al. explored the accuracy of their model. Overall, the model reproduces experimental results, but it is not yet perfect. The differences between the model and the experiments suggest new questions and tests that could advance our understanding of biology. In particular, Breuer et al. identified 30 genes that are essential for life in these cells but that currently have no known purpose. Continuing to develop and expand models like these to reproduce more complex living systems provides a tool to test current knowledge of biology. These models may become so advanced that they could predict how living things will respond to changing situations. This would allow scientists to test ideas sooner and make much faster progress in understanding life on Earth. Ultimately, these models could one day help to accelerate medical and industrial processes to save lives and enhance productivity.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Bacteriano / Genes Essenciais / Mycoplasma mycoides Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Bacteriano / Genes Essenciais / Mycoplasma mycoides Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article