Genome-scale metabolic modeling reveals key features of a minimal gene set.
Mesoplasma florum
genome design
genome-scale models
minimal cells
synthetic biology
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
18
06
2021
received:
16
11
2020
accepted:
22
06
2021
entrez:
21
7
2021
pubmed:
22
7
2021
medline:
14
1
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34288418
doi: 10.15252/msb.202010099
pmc: PMC8290834
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e10099Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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