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

• Published in: Biotechnology and bioengineering Vol. 91; no. 5; pp. 643 - 648
• Main Authors: Fong, Stephen S., Burgard, Anthony P., Herring, Christopher D., Knight, Eric M., Blattner, Frederick R., Maranas, Costas D., Palsson, Bernhard O.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 05.09.2005; Wiley; Wiley Subscription Services, Inc
• Subjects: Adaptation, Physiological; Bacteria; Biological and medical sciences; Biological Evolution; Biotechnology; computational model; Computer Simulation; Engineering; Escherichia coli; Escherichia coli - growth & development; Escherichia coli - metabolism; evolution; Fundamental and applied biological sciences. Psychology; Genome, Bacterial; Glucose; Glucose - metabolism; Kinetics; Lactic Acid - biosynthesis; metabolic engineering; Metabolism; Models, Biological; Temperature; Computer simulation; Escherichia coli; Production; computational model; Bacteria; Metabolic engineering; Models; Lactic acid; evolution; Enterobacteriaceae
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.20542

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. © 2005 Wiley Periodicals, Inc.