Enhancing sesquiterpene production in Saccharomyces cerevisiae through in silico driven metabolic engineering
Journal article, 2009
A genome-scale metabolic model was used to identify new target genes for enhanced biosynthesis of sesquiterpenes in the yeast Saccharomyces cerevisiae. The effect of gene deletions on the flux distributions in the metabolic model of S. cerevisiae was assessed using Opt Gene as the modeling framework and minimization of metabolic adjustments (MOMA) as objective function. Deletion of NADPH-dependent glutamate dehydrogenase encoded by GDH1 was identified as the best target gene for the improvement of sesquiterpene biosynthesis in yeast. Deletion of this gene enhances the available NADPH in the cytosol for other NADPH requiring enzymes, including HMG-CoA reductase. However, since disruption of GDH1 impairs the ammonia utilization, simultaneous over-expression of the NADH-dependent glutamate dehydrogenase en coded by GDH2 was also considered in this study. Deletion of GDH1 led to an approximately 85% increase in the final cubebol titer. However, deletion of this gene also caused a significant decrease in the maximum specific growth rate. Over-expression of GDH2 did not show a further effect on the final cubebol titer but this alteration significantly improved the growth rate compared to the GDH1 deleted strain. (C) 2009 Elsevier Inc. All rights reserved.
beta-carotene
food yeast
biosynthesis
Saccharomyces cerevisiae
Sesquiterpene
Isoprenoid
yeast candida-utilis
Glutamate dehydrogenase
ammonium
high-level production
assimilation
glutamate-dehydrogenase
lycopene
escherichia-coli
catabolite repression
NADPH availability
Minimization of metabolic adjustments
Flux balance analysis
Cubebol
In silico metabolic engineering
Author
M. A. Asadollahi
J. Maury
K. R. Patil
M. Schalk
A. Clark
Jens B Nielsen
Chalmers, Chemical and Biological Engineering, Life Sciences
Metabolic Engineering
1096-7176 (ISSN) 1096-7184 (eISSN)
Vol. 11 6 328-334Subject Categories
Microbiology
Areas of Advance
Life Science Engineering (2010-2018)
DOI
10.1016/j.ymben.2009.07.001