Genome‐scale metabolic modeling reveals key features of a minimal gene set. Issue 7 (20th July 2021)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Molecular systems biology. Volume 17:Issue 7(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-20
• Subjects: genome design -- genome‐scale models -- Mesoplasma florum -- minimal cells -- synthetic biology; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.202010099
• Languages: English
• ISSNs: 1744-4292

Abstract

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 i JL208 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 i JL208. Discrepancies between model predictions and observations were mechanistically explained using protein structures and network analysis. i JL208 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. i JL208 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 : 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.