» Articles » PMID: 33134082

Genome-scale Metabolic Reconstruction of the Non-model Yeast SD108 and Its Application to Organic Acids Production

Overview
Specialty Biochemistry
Date 2020 Nov 2
PMID 33134082
Citations 8
Authors
Affiliations
Soon will be listed here.
Abstract

Many platform chemicals can be produced from renewable biomass by microorganisms, with organic acids making up a large fraction. Intolerance to the resulting low pH growth conditions, however, remains a challenge for the industrial production of organic acids by microorganisms. SD108 is a promising host for industrial production because it is tolerant to acidic conditions as low as pH 2.0. With the goal to systematically assess the metabolic capabilities of this non-model yeast, we developed a genome-scale metabolic model for SD108 spanning 850 genes, 1826 reactions, and 1702 metabolites. In order to improve the model's quantitative predictions, organism-specific macromolecular composition and ATP maintenance requirements were determined experimentally and implemented. We examined its network topology, including essential genes and flux coupling analysis and drew comparisons with the Yeast 8.3 model for . We explored the carbon substrate utilization and examined the organism's production potential for the industrially-relevant succinic acid, making use of the OptKnock framework to identify gene knockouts which couple production of the targeted chemical to biomass production. The genome-scale metabolic model 850 is a data-supported curated model which can inform genetic interventions for overproduction.

Citing Articles

Genome-Scale Metabolic Models in Fungal Pathogens: Past, Present, and Future.

Fonseca-Fernandez A, Gonzalez Barrios A, Ramirez A Int J Mol Sci. 2024; 25(19).

PMID: 39409179 PMC: 11476900. DOI: 10.3390/ijms251910852.


Mitochondrial ATP generation is more proteome efficient than glycolysis.

Shen Y, Dinh H, Cruz E, Chen Z, Bartman C, Xiao T Nat Chem Biol. 2024; 20(9):1123-1132.

PMID: 38448734 DOI: 10.1038/s41589-024-01571-y.


Reconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica.

Cui Z, Zhong Y, Sun Z, Jiang Z, Deng J, Wang Q Nat Commun. 2023; 14(1):8480.

PMID: 38123538 PMC: 10733433. DOI: 10.1038/s41467-023-44245-4.


An end-to-end pipeline for succinic acid production at an industrially relevant scale using Issatchenkia orientalis.

Tran V, Mishra S, Bhagwat S, Shafaei S, Shen Y, Allen J Nat Commun. 2023; 14(1):6152.

PMID: 37788990 PMC: 10547785. DOI: 10.1038/s41467-023-41616-9.


Metabolic engineering of low-pH-tolerant non-model yeast, , for production of citramalate.

Wu Z, Sun W, Shen Y, Pratas J, Suthers P, Hsieh P Metab Eng Commun. 2023; 16:e00220.

PMID: 36860699 PMC: 9969067. DOI: 10.1016/j.mec.2023.e00220.


References
1.
Kavscek M, Bhutada G, Madl T, Natter K . Optimization of lipid production with a genome-scale model of Yarrowia lipolytica. BMC Syst Biol. 2015; 9:72. PMC: 4623914. DOI: 10.1186/s12918-015-0217-4. View

2.
Barua D, Kim J, Reed J . An automated phenotype-driven approach (GeneForce) for refining metabolic and regulatory models. PLoS Comput Biol. 2010; 6(10):e1000970. PMC: 2965739. DOI: 10.1371/journal.pcbi.1000970. View

3.
Koonin E, Fedorova N, Jackson J, Jacobs A, Krylov D, Makarova K . A comprehensive evolutionary classification of proteins encoded in complete eukaryotic genomes. Genome Biol. 2004; 5(2):R7. PMC: 395751. DOI: 10.1186/gb-2004-5-2-r7. View

4.
Martinez I, Bennett G, San K . Metabolic impact of the level of aeration during cell growth on anaerobic succinate production by an engineered Escherichia coli strain. Metab Eng. 2010; 12(6):499-509. DOI: 10.1016/j.ymben.2010.09.002. View

5.
Feist A, Herrgard M, Thiele I, Reed J, Palsson B . Reconstruction of biochemical networks in microorganisms. Nat Rev Microbiol. 2009; 7(2):129-43. PMC: 3119670. DOI: 10.1038/nrmicro1949. View