Genome‐scale metabolic modeling reveals key features of a minimal gene set
Abstract 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%...
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-07-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.202010099 |
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| author | Jean‐Christophe Lachance Dominick Matteau Joëlle Brodeur Colton J Lloyd Nathan Mih Zachary A King Thomas F Knight Adam M Feist Jonathan M Monk Bernhard O Palsson Pierre‐Étienne Jacques Sébastien Rodrigue |
| author_facet | Jean‐Christophe Lachance Dominick Matteau Joëlle Brodeur Colton J Lloyd Nathan Mih Zachary A King Thomas F Knight Adam M Feist Jonathan M Monk Bernhard O Palsson Pierre‐Étienne Jacques Sébastien Rodrigue |
| author_sort | Jean‐Christophe Lachance |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-ffd50eb1a2234bef84adfb826296e9f3 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2021-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-ffd50eb1a2234bef84adfb826296e9f32025-08-24T12:01:09ZengSpringer NatureMolecular Systems Biology1744-42922021-07-0117712010.15252/msb.202010099Genome‐scale metabolic modeling reveals key features of a minimal gene setJean‐Christophe Lachance0Dominick Matteau1Joëlle Brodeur2Colton J Lloyd3Nathan Mih4Zachary A King5Thomas F Knight6Adam M Feist7Jonathan M Monk8Bernhard O Palsson9Pierre‐Étienne Jacques10Sébastien Rodrigue11Département de Biologie, Université de SherbrookeDépartement de Biologie, Université de SherbrookeDépartement de Biologie, Université de SherbrookeDepartment of Bioengineering, University of CaliforniaDepartment of Bioengineering, University of CaliforniaDepartment of Bioengineering, University of CaliforniaGinkgo BioworksDepartment of Bioengineering, University of CaliforniaDepartment of Bioengineering, University of CaliforniaDepartment of Bioengineering, University of CaliforniaDépartement de Biologie, Université de SherbrookeDépartement de Biologie, Université de SherbrookeAbstract 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.https://doi.org/10.15252/msb.202010099genome designgenome‐scale modelsMesoplasma florumminimal cellssynthetic biology |
| spellingShingle | Jean‐Christophe Lachance Dominick Matteau Joëlle Brodeur Colton J Lloyd Nathan Mih Zachary A King Thomas F Knight Adam M Feist Jonathan M Monk Bernhard O Palsson Pierre‐Étienne Jacques Sébastien Rodrigue Genome‐scale metabolic modeling reveals key features of a minimal gene set Molecular Systems Biology genome design genome‐scale models Mesoplasma florum minimal cells synthetic biology |
| title | Genome‐scale metabolic modeling reveals key features of a minimal gene set |
| title_full | Genome‐scale metabolic modeling reveals key features of a minimal gene set |
| title_fullStr | Genome‐scale metabolic modeling reveals key features of a minimal gene set |
| title_full_unstemmed | Genome‐scale metabolic modeling reveals key features of a minimal gene set |
| title_short | Genome‐scale metabolic modeling reveals key features of a minimal gene set |
| title_sort | genome scale metabolic modeling reveals key features of a minimal gene set |
| topic | genome design genome‐scale models Mesoplasma florum minimal cells synthetic biology |
| url | https://doi.org/10.15252/msb.202010099 |
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