In silico design and adaptive evolution of Escherichia coli for production of lactic acid

Stephen S. Fong; Anthony P. Burgard; Christopher D. Herring; Eric M. Knight; Frederick R. Blattner; Costas D. Maranas; Bernhard O. Palsson

doi:10.1002/bit.20542

In silico design and adaptive evolution of Escherichia coli for production of lactic acid

Stephen S. Fong, Anthony P. Burgard, Christopher D. Herring, Eric M. Knight, Frederick R. Blattner, Costas D. Maranas, Bernhard O. Palsson^*

^*Corresponding author for this work

University of Iceland

Research output: Contribution to journal › Article › peer-review

286 Citations (Scopus)

Abstract

The development and validation of new methods to help direct rational strain design for metabolite overproduction remains an important problem in metabolic engineering. Here we show that computationally predicted E. coli strain designs, calculated from a genome-scale metabolic model, can lead to successful production strains and that adaptive evolution of the engineered strains can lead to improved production capabilities. Three strain designs for lactate production were implemented yielding a total of 11 evolved production strains that were used to demonstrate the utility of this integrated approach. Strains grown on 2 g/L glucose at 37°C showed lactate titers ranging from 0.87 to 1.75 g/L and secretion rates that were directly coupled to growth rates.

Original language	English
Pages (from-to)	643-648
Number of pages	6
Journal	Biotechnology and Bioengineering
Volume	91
Issue number	5
DOIs	https://doi.org/10.1002/bit.20542
Publication status	Published - 5 Sept 2005

Other keywords

Computational model
Escherichia coli
Evolution
Metabolic engineering

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title = "In silico design and adaptive evolution of Escherichia coli for production of lactic acid",

abstract = "The development and validation of new methods to help direct rational strain design for metabolite overproduction remains an important problem in metabolic engineering. Here we show that computationally predicted E. coli strain designs, calculated from a genome-scale metabolic model, can lead to successful production strains and that adaptive evolution of the engineered strains can lead to improved production capabilities. Three strain designs for lactate production were implemented yielding a total of 11 evolved production strains that were used to demonstrate the utility of this integrated approach. Strains grown on 2 g/L glucose at 37°C showed lactate titers ranging from 0.87 to 1.75 g/L and secretion rates that were directly coupled to growth rates.",

keywords = "Computational model, Escherichia coli, Evolution, Metabolic engineering",

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AU - Fong, Stephen S.

AU - Burgard, Anthony P.

AU - Herring, Christopher D.

AU - Knight, Eric M.

AU - Blattner, Frederick R.

AU - Maranas, Costas D.

AU - Palsson, Bernhard O.

PY - 2005/9/5

Y1 - 2005/9/5

N2 - The development and validation of new methods to help direct rational strain design for metabolite overproduction remains an important problem in metabolic engineering. Here we show that computationally predicted E. coli strain designs, calculated from a genome-scale metabolic model, can lead to successful production strains and that adaptive evolution of the engineered strains can lead to improved production capabilities. Three strain designs for lactate production were implemented yielding a total of 11 evolved production strains that were used to demonstrate the utility of this integrated approach. Strains grown on 2 g/L glucose at 37°C showed lactate titers ranging from 0.87 to 1.75 g/L and secretion rates that were directly coupled to growth rates.

AB - The development and validation of new methods to help direct rational strain design for metabolite overproduction remains an important problem in metabolic engineering. Here we show that computationally predicted E. coli strain designs, calculated from a genome-scale metabolic model, can lead to successful production strains and that adaptive evolution of the engineered strains can lead to improved production capabilities. Three strain designs for lactate production were implemented yielding a total of 11 evolved production strains that were used to demonstrate the utility of this integrated approach. Strains grown on 2 g/L glucose at 37°C showed lactate titers ranging from 0.87 to 1.75 g/L and secretion rates that were directly coupled to growth rates.

KW - Computational model

KW - Escherichia coli

KW - Evolution

KW - Metabolic engineering

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EP - 648

JO - Biotechnology and Bioengineering

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In silico design and adaptive evolution of Escherichia coli for production of lactic acid

Abstract

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