Search: id:"swepub:oai:research.chalmers.se:86625f71-87f8-468e-8b43-3e97eeaf44c8" >
Genome-scale modeli...
Genome-scale modeling drives 70-fold improvement of intracellular heme production in Saccharomyces cerevisiae
-
- Ishchuk, Olena, 1980 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
-
- Domenzain Del Castillo Cerecer, Iván, 1991 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation
-
- Sánchez, Benjamín José, 1988 (author)
- Danmarks Tekniske Universitet,Technical University of Denmark,Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology
-
show more...
-
- Muniz, Facundo, 1987 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
-
- Martinez Ruiz, Jose Luis, 1981 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Danmarks Tekniske Universitet,Technical University of Denmark
-
- Nielsen, Jens B, 1962 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,BioInnovation Institute (BII),Novo Nordisk Fonden,Novo Nordisk Foundation
-
- Petranovic Nielsen, Dina, 1975 (author)
- Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology
-
show less...
-
(creator_code:org_t)
- 2022-07-18
- 2022
- English.
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
- Related links:
-
https://research.cha... (primary) (free)
-
show more...
-
https://research.cha...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Heme is an oxygen carrier and a cofactor of both industrial enzymes and food additives. The intracellular level of free heme is low, which limits the synthesis of heme proteins. Therefore, increasing heme synthesis allows an increased production of heme proteins. Using the genome-scale metabolic model (GEM) Yeast8 for the yeast Saccharomyces cerevisiae, we identified fluxes potentially important to heme synthesis. With this model, in silico simulations highlighted 84 gene targets for balancing biomass and increasing heme production. Of those identified, 76 genes were individually deleted or overexpressed in experiments. Empirically, 40 genes individually increased heme production (up to threefold). Heme was increased by modifying target genes, which not only included the genes involved in heme biosynthesis, but also those involved in glycolysis, pyruvate, Fe-S clusters, glycine, and succinyl-coenzyme A (CoA) metabolism. Next, we developed an algorithmic method for predicting an optimal combination of these genes by using the enzyme-constrained extension of the Yeast8 model, ecYeast8. The computationally identified combination for enhanced heme production was evaluated using the heme ligand-binding biosensor (Heme-LBB). The positive targets were combined using CRISPR-Cas9 in the yeast strain (IMX581-HEM15-HEM14-HEM3- δshm1-HEM2-δhmx1-FET4-δgcv2-HEM1-δgcv1-HEM13), which produces 70-foldhigher levels of intracellular heme.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Biokatalys och enzymteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Biocatalysis and Enzyme Technology (hsv//eng)
Keyword
- Genome-scale modeling
- heme ligand-binding biosensor
- metabolic engineering
- heme
- Saccharomyces cerevisiae
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database