ArticleMolecular systems biology2021
Model-guided development of an evolutionarily stable yeast chassis.
Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Dynamic, model-guided intensification of fuel ethanol production in yeast: proteome constraints, CRISPR rewiring, and high-gravity fermentations.Archives of microbiology · 2026Review
- Yeast Stress Response to Synthetic Constructs.ACS synthetic biology · 2026Review
- Genome-scale prediction of gene ontology from mass fingerprints reveals new metabolic gene functions.Life science alliance · 2025Article
- From genetic constraints to process hurdles: A review ofCurrent research in food science · 2025Review
- Inducible Synthetic Growth Regulation Using the ClpXP Proteasome Enhances cis,cis-Muconic Acid and Glycolic Acid Yields inACS synthetic biology · 2023Article
- Optogenetic control of beta-carotene bioproduction in yeast across multiple lab-scales.Frontiers in bioengineering and biotechnology · 2023Article
- Predictive evolution of metabolic phenotypes using model-designed environments.Molecular systems biology · 2022Article
- Genome-scale modeling of yeast metabolism: retrospectives and perspectives.FEMS yeast research · 2022Review
- In vivo, in vitro and in silico: an open space for the development of microbe-based applications of synthetic biology.Microbial biotechnology · 2022Article
- Model-guided development of an evolutionarily stable yeast chassis.Molecular systems biology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
First-principle metabolic modelling holds potential for designing microbial chassis that are resilient against phenotype reversal due to adaptive mutations. Yet, the theory of model-based chassis design has rarely been put to rigorous experimental test. Here, we report the development of Saccharomyces cerevisiae chassis strains for dicarboxylic acid production using genome-scale metabolic modelling. The chassis strains, albeit geared for higher flux towards succinate, fumarate and malate, do not appreciably secrete these metabolites. As predicted by the model, introducing product-specific TCA cycle disruptions resulted in the secretion of the corresponding acid. Adaptive laboratory evolution further improved production of succinate and fumarate, demonstrating the evolutionary robustness of the engineered cells. In the case of malate, multi-omics analysis revealed a flux bypass at peroxisomal malate dehydrogenase that was missing in the yeast metabolic model. In all three cases, flux balance analysis integrating transcriptomics, proteomics and metabolomics data confirmed the flux re-routing predicted by the model. Taken together, our modelling and experimental results have implications for the computer-aided design of microbial cell factories.
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