Yeast engineering for pharmaceutical and nutraceutical purposes
type: CreativeWork
description: Saccharomyces is a genus of fungi consisting of many species of yeast strains including S. cerevisiae and S. boulardii, and has been engineered for implementing economic processes for producing biofuels and chemicals. However, this microorganism has restricted capabilities for producing other biomolecules than ethanol due to a rigid metabolic flux through glycolysis and ethanol pathway during utilization of fermentable sugars. Since the ethanol pathway plays a key role in cytosolic acetyl-CoA synthesis and redox balance of Saccharomyces, new metabolic engineering approaches not to knock out its ethanol pathway but to minimize the overflow metabolism are needed for increasing productivities of acetyl-CoA derivatives, growth-dependent metabolites, and intracellular biomolecules. The overall goal of my thesis study is to manipulate sugar metabolisms in Saccharomyces yeast strains for developing optimal yeast cells capable of efficiently synthesizing value-added pharmaceutical and nutraceutical molecules by bypassing negative characteristics of the overflow metabolism. Two strategies for bypassing the native overflow metabolism in Saccharomyces are demonstrated in this study: i) utilization of non-fermentable sugar, and ii) elimination of the interaction between phosphofructokinase and fructose 2,6-bisphosphate. Xylose utilization allowed engineered S. cerevisiae to dysregulate glucose-dependent repressions on cytosolic acetyl-CoA synthesis, ethanol re-oxidation, and oxidative phosphorylation. Restoring transcription levels of these metabolisms in engineered yeasts led to efficient cytosolic acetyl-CoA synthesis by simultaneous co-utilization of xylose and ethanol. The positive xylose effect was expanded to both accumulative and diffusible isoprenoids, which are synthesized from cytosolic acetyl-CoA. The elimination of allosteric up-regulation on phosphofructokinase and consequently upper glycolysis down-regulation could be achieved by mutagenesis on PFK1 and PFK2 or de…
abstract: Saccharomyces is a genus of fungi consisting of many species of yeast strains including S. cerevisiae and S. boulardii, and has been engineered for implementing economic processes for producing biofuels and chemicals. However, this microorganism has restricted capabilities for producing other biomolecules than ethanol due to a rigid metabolic flux through glycolysis and ethanol pathway during utilization of fermentable sugars. Since the ethanol pathway plays a key role in cytosolic acetyl-CoA synthesis and redox balance of Saccharomyces, new metabolic engineering approaches not to knock out its ethanol pathway but to minimize the overflow metabolism are needed for increasing productivities of acetyl-CoA derivatives, growth-dependent metabolites, and intracellular biomolecules. The overall goal of my thesis study is to manipulate sugar metabolisms in Saccharomyces yeast strains for developing optimal yeast cells capable of efficiently synthesizing value-added pharmaceutical and nutraceutical molecules by bypassing negative characteristics of the overflow metabolism. Two strategies for bypassing the native overflow metabolism in Saccharomyces are demonstrated in this study: i) utilization of non-fermentable sugar, and ii) elimination of the interaction between phosphofructokinase and fructose 2,6-bisphosphate. Xylose utilization allowed engineered S. cerevisiae to dysregulate glucose-dependent repressions on cytosolic acetyl-CoA synthesis, ethanol re-oxidation, and oxidative phosphorylation. Restoring transcription levels of these metabolisms in engineered yeasts led to efficient cytosolic acetyl-CoA synthesis by simultaneous co-utilization of xylose and ethanol. The positive xylose effect was expanded to both accumulative and diffusible isoprenoids, which are synthesized from cytosolic acetyl-CoA. The elimination of allosteric up-regulation on phosphofructokinase and consequently upper glycolysis down-regulation could be achieved by mutagenesis on PFK1 and PFK2 or de…
author: Kwak, Suryang
language: en
keywords: Saccharomyces cerevisiae, Saccharomyces boulardii, Acetyl-Coenzyme A (Acetyl-CoA), Isoprenoid, Cofactor, Guanosine diphosphate mannose (GDP-mannose), Mannan oligosaccharide
date published: 2017-08-10T19:52:14Z
date modified: 2026-07-22T22:24:34Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/97609