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A metabolic and genomic study of engineered Saccharomyces cerevisiae strains for high glycerol production

Paper ID Volume ID Publish Year Pages File Format Full-Text
31971 44862 2007 15 PDF Available
Title
A metabolic and genomic study of engineered Saccharomyces cerevisiae strains for high glycerol production
Abstract

Towards a global objective to produce chemical derivatives by microbial processes, this work dealt with a metabolic engineering of the yeast Saccharomyces cerevisiae for glycerol production. To accomplish this goal, overexpression of GPD1 was introduced in a tpi1Δ mutant defective in triose phosphate isomerase. This strategy alleviated the inositol-less phenotype of this mutant, by reducing the levels of dihydroxyacetone phosphate and glycerol-3-P, two potent inhibitors of myo-inositol synthase that catalyzes the formation of inositol-6-phosphate from glucose-6-phosphate. Further deletion of ADH1 and overexpression of ALD3, encoding, respectively, the major NAD+-dependent alcohol dehydrogenase and a cytosolic NAD+-dependent aldehyde dehydrogenase yielded a yeast strain able to produce 0.46 g glycerol (g glucose)−1 at a maximal rate of 3.1 mmol (g dry mass)−1 h−1 in aerated batch cultures. At the metabolic level, this genetic strategy shifted the flux control coefficient of the pathway to the level of the glycerol efflux, with a consequent intracellular accumulation of glycerol that could be partially reduced by the overproduction of glycerol exporter encoded by FPS1. At the transcriptomic level, this metabolic reprogramming brought about the upregulation of genes encoding NAD+/NADP+ binding proteins, a partial derepression of genes coding for TCA cycle and respiratory enzymes, and a downregulation of genes implicated in protein biosynthesis and ribosome biogenesis. Altogether, these metabolic and molecular alterations stand for major hurdles that may represent potential targets for further optimizing glycerol production in yeast.

Keywords
Glycerol metabolism; Genetic engineering; Metabolic regulation; Transcriptomic analysis; Saccharomyces cerevisiae
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A metabolic and genomic study of engineered Saccharomyces cerevisiae strains for high glycerol production
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 9, Issue 4, July 2007, Pages 364–378
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us