Application of mathematical tools for metabolic design of microbial ethanol production

Biotechnology and Bioengineering
V HatzimanikatisJ E Bailey

Abstract

Many attempts to engineer cellular metabolism have failed due to the complexity of cellular functions. Mathematical and computational methods are needed that can organize the available experimental information, and provide insight and guidance for successful metabolic engineering. Two such methods are reviewed here. Both methods employ a (log)linear kinetic model of metabolism that is constructed based on enzyme kinetics characteristics. The first method allows the description of the dynamic responses of metabolic systems subject to spatiotemporal variations in their parameters. The second method considers the product-oriented, constrained optimization of metabolic reaction networks using mixed-integer linear programming methods. The optimization framework is used in order to identify the combinations of the metabolic characteristics of the glycolytic enzymes from yeast and bacteria that will maximize ethanol production. The methods are also applied to the design of microbial ethanol production metabolism. The results of the calculations are in qualitative agreement with experimental data presented here. Experiments and calculations suggest that, in resting Escherichia coli cells, ethanol production and glucose uptake rates can...Continue Reading

References

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Citations

Apr 27, 2010·PLoS Computational Biology·Sridhar RanganathanCostas D Maranas
Feb 18, 2011·BMC Systems Biology·Vinay Satish KumarCostas D Maranas
Dec 14, 2004·Nature Biotechnology·Jeong-Sun SeoHyen Sam Kang
Jul 22, 2010·Trends in Biotechnology·Ljubisa Miskovic, Vassily Hatzimanikatis
Jun 5, 2004·Journal of Theoretical Biology·Sharon J WibackBernhard Ø Palsson
Sep 27, 2014·IET Systems Biology·Michael A Henson, Timothy J Hanly
Aug 10, 2000·Metabolic Engineering·J Varner, D Ramkrishna
Oct 20, 2004·Metabolic Engineering·Diana VisserJoseph J Heijnen
Jun 15, 2014·Metabolic Engineering·Ali KhodayariCostas D Maranas
Mar 4, 2014·PLoS Computational Biology·Anupam ChowdhuryCostas D Maranas
Nov 5, 2003·Biotechnology and Bioengineering·Anthony P BurgardCostas D Maranas
Sep 5, 2002·Biotechnology and Bioengineering·Vassily Hatzimanikatis, James C Liao
Sep 16, 2006·Biotechnology and Bioengineering·Fredrick O AbokaJoseph J Heijnen
Jan 24, 2007·Biotechnology and Bioengineering·Jared L HjerstedRadhakrishnan Mahadevan
Oct 16, 2001·Critical Reviews in Biotechnology·P R Patnaik
Apr 21, 1999·Current Opinion in Biotechnology·J Varner, D Ramkrishna

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