Publications by authors named "Anshu Deewan"

3 Publications

  • Page 1 of 1

Investigating the role of the transcriptional regulator Ure2 on the metabolism of Saccharomyces cerevisiae: a multi-omics approach.

Appl Microbiol Biotechnol 2021 Jun 21;105(12):5103-5112. Epub 2021 Jun 21.

DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Ure2 regulates nitrogen catabolite repression in Saccharomyces cerevisiae. Deletion of URE2 induces a physiological state mimicking the nitrogen starvation and autophagic responses. Previous work has shown that deletion of URE2 increases the fermentation rate of some wine-producing strains of S. cerevisiae. In this work, we investigated the effect of URE2 deletion (ΔURE2) on the metabolism of S. cerevisiae. During growth on glucose, the ΔURE2 mutant grew at a 40% slower rate than the wild type; however, it produced ethanol at a 31% higher rate. To better under the behavior of this mutant, we performed transcriptomics and metabolomics. Analysis of the RNA sequencing results and metabolite levels indicates that the mutant strain exhibited characteristics of both nitrogen starvation and autophagy, including the upregulation of allantoin, urea, and amino acid uptake and utilization pathways and selective autophagic machinery. In addition, pyruvate decarboxylase and alcohol dehydrogenase isoforms were expressed at higher rates than the wild type. The mutant also accumulated less trehalose and glycogen, and produced more lipids. The induction of a nitrogen starvation-like state and increase in lipid production in nitrogen-rich conditions suggest that URE2 may be a promising target for metabolic engineering in S. cerevisiae and other yeasts for the production of lipids and lipid-derived compounds. KEY POINTS: • Deletion of URE2 increases ethanol and lipid production in Saccharomyces cerevisiae. • Deletion of URE2 reduces glycogen and trehalose production. • Metabolic changes mimic nitrogen starvation and autophagic response.
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http://dx.doi.org/10.1007/s00253-021-11394-9DOI Listing
June 2021

A comprehensive genome-scale model for IFO0880 accounting for functional genomics and phenotypic data.

Metab Eng Commun 2019 Dec 28;9:e00101. Epub 2019 Aug 28.

Department of Chemical Engineering, The Pennsylvania State University, University Park, 306 Chemical and Biomedical Engineering Building, PA, 16802-4400, USA.

is a red, basidiomycetes yeast that can accumulate a large amount of lipids and produce carotenoids. To better assess this non-model yeast's metabolic capabilities, we reconstructed a genome-scale model of IFO0880's metabolic network (1108) accounting for 2204 reactions, 1985 metabolites and 1108 genes. In this work, we integrated and supplemented the current knowledge with in-house generated biomass composition and experimental measurements pertaining to the organism's metabolic capabilities. Predictions of genotype-phenotype relations were improved through manual curation of gene-protein-reaction rules for 543 reactions leading to correct recapitulations of 84.5% of gene essentiality data (sensitivity of 94.3% and specificity of 53.8%). Organism-specific macromolecular composition and ATP maintenance requirements were experimentally measured for two separate growth conditions: (i) carbon and (ii) nitrogen limitations. Overall, 1108 reproduced 's utilization capabilities for 18 alternate substrates, matched measured wild-type growth yield, and recapitulated the viability of 772 out of 819 deletion mutants. As a demonstration to the model's fidelity in guiding engineering interventions, the OptForce procedure was applied on 1108 for triacylglycerol overproduction. Suggested interventions recapitulated many of the previous successful implementations of genetic modifications and put forth a few new ones.
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http://dx.doi.org/10.1016/j.mec.2019.e00101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838544PMC
December 2019

pH selectively regulates citric acid and lipid production in Yarrowia lipolytica W29 during nitrogen-limited growth on glucose.

J Biotechnol 2019 Jan 26;290:10-15. Epub 2018 Nov 26.

Department of Chemical and Biomolecular Engineering, DOE Center for Advanced Bioenergy and Bioproducts Innovation, Carl R. Woese Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. Electronic address:

Yarrowia lipolytica has been used to produce both citric acid and lipid-based bioproducts at high titers. In this study, we found that pH differentially affects citric acid and lipid production in Y. lipolytica W29, with citric acid production enhanced at more neutral pH's and lipid production enhanced at more acid pH's. To determine the mechanism governing this pH-dependent switch between citric acid and lipid production, we profiled gene expression at different pH's and found that the relative expression of multiple transporters is increased at neutral pH. These results suggest that this pH-dependent switch is mediated at the level of citric acid transport rather than changes in the expression of the enzymes involved in citric acid and lipid metabolism. In further support of this mechanism, thermodynamic calculations suggest that citric acid secretion is more energetically favorable at neutral pH's, assuming the fully protonated acid is the substrate for secretion. Collectively, these results provide new insights regarding citric acid and lipid production in Y. lipolytica and may offer new strategies for metabolic engineering and process design.
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http://dx.doi.org/10.1016/j.jbiotec.2018.10.012DOI Listing
January 2019
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