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Title: Essential metabolism for a minimal cell

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.

Authors:
ORCiD logo [1]; ORCiD logo [1];  [2];  [2];  [2];  [2];  [2];  [2];  [3];  [3];  [4];  [4];  [5];  [1];  [2]; ORCiD logo [1]
  1. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States
  2. J Craig Venter Institute, La Jolla, United States
  3. Department of Pharmacology and School of Pharmacy, University of California at San Diego, La Jolla, United States
  4. Department of Microbiology and Cell Science, University of Florida, Gainesville, United States
  5. Horticultural Sciences Department, University of Florida, Gainesville, United States
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1507449
Alternate Identifier(s):
OSTI ID: 1507450
Grant/Contract Number:  
ORNL 4000134575
Resource Type:
Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Name: eLife Journal Volume: 8; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English

Citation Formats

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., and Luthey-Schulten, Zaida. Essential metabolism for a minimal cell. United States: N. p., 2019. Web. doi:10.7554/eLife.36842.
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. Essential metabolism for a minimal cell. United States. doi:10.7554/eLife.36842.
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., and Luthey-Schulten, Zaida. Fri . "Essential metabolism for a minimal cell". United States. doi:10.7554/eLife.36842.
@article{osti_1507449,
title = {Essential metabolism for a minimal cell},
author = {Breuer, Marian and Earnest, Tyler M. and Merryman, Chuck and Wise, Kim S. and Sun, Lijie and Lynott, Michaela R. and Hutchison, Clyde A. and Smith, Hamilton O. and Lapek, John D. and Gonzalez, David J. and de Crécy-Lagard, Valérie and Haas, Drago and Hanson, Andrew D. and Labhsetwar, Piyush and Glass, John I. and Luthey-Schulten, Zaida},
abstractNote = {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.},
doi = {10.7554/eLife.36842},
journal = {eLife},
number = ,
volume = 8,
place = {United States},
year = {2019},
month = {1}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.7554/eLife.36842

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