| Autor: |
Lachance, Jean‐Christophe, Matteau, Dominick, Brodeur, Joëlle, Lloyd, Colton J, Mih, Nathan, King, Zachary A, Knight, Thomas F, Feist, Adam M, Monk, Jonathan M, Palsson, Bernhard O, Jacques, Pierre‐Étienne, Rodrigue, Sébastien |
| Předmět: |
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| Zdroj: |
Molecular Systems Biology; Jul2021, Vol. 17 Issue 7, p1-20, 20p |
| Abstrakt: |
Mesoplasma florum, a fast‐growing near‐minimal organism, is a compelling model to explore rational genome designs. Using sequence and structural homology, the set of metabolic functions its genome encodes was identified, allowing the reconstruction of a metabolic network representing ˜ 30% of its protein‐coding genes. Growth medium simplification enabled substrate uptake and product secretion rate quantification which, along with experimental biomass composition, were integrated as species‐specific constraints to produce the functional iJL208 genome‐scale model (GEM) of metabolism. Genome‐wide expression and essentiality datasets as well as growth data on various carbohydrates were used to validate and refine iJL208. Discrepancies between model predictions and observations were mechanistically explained using protein structures and network analysis. iJL208 was also used to propose an in silico reduced genome. Comparing this prediction to the minimal cell JCVI‐syn3.0 and its parent JCVI‐syn1.0 revealed key features of a minimal gene set. iJL208 is a stepping‐stone toward model‐driven whole‐genome engineering. SYNOPSIS: The first genome‐scale metabolic model for the near‐minimal bacterium Mesoplasma florum is reported. Comparing the model‐driven prediction of a M. florum genome reduction scenario to a closely related minimal cell reveals key features of a minimal gene set. iJL208, the first genome‐scale metabolic model for the near‐minimal organism Mesoplasma florum, comprises 370 reactions and accounts for ˜ 30% of the total gene count in the genome.Model‐driven predictions are validated through the integration of extensive experimental data, including gene expression datasets and growth phenotypes on various sugars.A robust M. florum genome reduction scenario is predicted using gene essentiality data and transcription units, resulting in a minimal genome containing 535 protein‐coding genes.A detailed comparison of this prediction to the phylogenetically related minimal cell JCVI‐syn3.0 reveals key features of a minimal gene set. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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