ArticleGenetics2009
Systems-level engineering of nonfermentative metabolism in yeast.
Article in Genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Efficient genome editing in filamentous fungi via an improved CRISPR-Cas9 ribonucleoprotein method facilitated by chemical reagents.Microbial biotechnology · 2021Article
- Rewired cellular signaling coordinates sugar and hypoxic responses for anaerobic xylose fermentation in yeast.PLoS genetics · 2019Article
- Comparative Analysis of Yeast Metabolic Network Models Highlights Progress, Opportunities for Metabolic Reconstruction.PLoS computational biology · 2015Article
- Contemplating 3-Hydroxypropionic Acid Biosynthesis in Klebsiella pneumoniae.Indian journal of microbiology · 2015Review
- Systems Biology of Microbial Exopolysaccharides Production.Frontiers in bioengineering and biotechnology · 2015Review
- Identification and treatment of heme depletion attributed to overexpression of a lineage of evolved P450 monooxygenases.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- A BioBrick compatible strategy for genetic modification of plants.Journal of biological engineering · 2012Article
- Production of 2,3-butanediol in Saccharomyces cerevisiae by in silico aided metabolic engineering.Microbial cell factories · 2012Article
- Parts plus pipes: synthetic biology approaches to metabolic engineering.Metabolic engineering · 2012Review
- Constraining the metabolic genotype-phenotype relationship using a phylogeny of in silico methods.Nature reviews. Microbiology · 2012Review
- Engineering strategy of yeast metabolism for higher alcohol production.Microbial cell factories · 2011Article
- Statistics-based model for prediction of chemical biosynthesis yield from Saccharomyces cerevisiae.Microbial cell factories · 2011Article
- Aspergillus fumigatus AcuM regulates both iron acquisition and gluconeogenesis.Molecular microbiology · 2010Article
- Harnessing nature's toolbox: regulatory elements for synthetic biology.Journal of the Royal Society, Interface · 2009Review
- Modular electron transfer circuits for synthetic biology: insulation of an engineered biohydrogen pathway.Bioengineered bugsArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We designed and experimentally validated an in silico gene deletion strategy for engineering endogenous one-carbon (C1) metabolism in yeast. We used constraint-based metabolic modeling and computer-aided gene knockout simulations to identify five genes (ALT2, FDH1, FDH2, FUM1, and ZWF1), which, when deleted in combination, predicted formic acid secretion in Saccharomyces cerevisiae under aerobic growth conditions. Once constructed, the quintuple mutant strain showed the predicted increase in formic acid secretion relative to a formate dehydrogenase mutant (fdh1 fdh2), while formic acid secretion in wild-type yeast was undetectable. Gene expression and physiological data generated post hoc identified a retrograde response to mitochondrial deficiency, which was confirmed by showing Rtg1-dependent NADH accumulation in the engineered yeast strain. Formal pathway analysis combined with gene expression data suggested specific modes of regulation that govern C1 metabolic flux in yeast. Specifically, we identified coordinated transcriptional regulation of C1 pathway enzymes and a positive flux control coefficient for the branch point enzyme 3-phosphoglycerate dehydrogenase (PGDH). Together, these results demonstrate that constraint-based models can identify seemingly unrelated mutations, which interact at a systems level across subcellular compartments to modulate flux through nonfermentative metabolic pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.