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Applied and Environmental Microbiology, July 2007, p. 4639-4647, Vol. 73, No. 14
0099-2240/07/$08.00+0     doi:10.1128/AEM.00527-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Metabolic Characterization of Escherichia coli Strains Adapted to Growth on Lactate

Qiang Hua,¹ Andrew R. Joyce,² Bernhard Ø. Palsson,^1* and Stephen S. Fong^1,

Department of Bioengineering, University of California, San Diego, La Jolla, California,¹ Bioinformatics Program, University of San Diego, La Jolla, California²

Received 7 March 2007/ Accepted 15 May 2007

In comparison with intensive studies of genetic mechanisms related to biological evolutionary systems, much less analysis has been conducted on metabolic network responses to adaptive evolution that are directly associated with evolved metabolic phenotypes. Metabolic mechanisms involved in laboratory evolution of Escherichia coli on gluconeogenic carbon sources, such as lactate, were studied based on intracellular flux states determined from ¹³C tracer experiments and ¹³C-constrained flux analysis. At the end point of laboratory evolution, strains exhibited a more than doubling of the average growth rate and a 50% increase in the average biomass yield. Despite different evolutionary trajectories among parallel evolved populations, most improvements were obtained within the first 250 generations of evolution and were generally characterized by a significant increase in pathway capacity. Partitioning between gluconeogenic and pyruvate catabolic flux at the pyruvate node remained almost unchanged, while flux distributions around the key metabolites phosphoenolpyruvate, oxaloacetate, and acetyl-coenzyme A were relatively flexible over the course of evolution on lactate to meet energetic and anabolic demands during rapid growth on this gluconeogenic carbon substrate. There were no clear qualitative correlations between most transcriptional expression and metabolic flux changes, suggesting complex regulatory mechanisms at multiple levels of genetics and molecular biology. Moreover, higher fitness gains for cell growth on both evolutionary and alternative carbon sources were found for strains that adaptively evolved on gluconeogenic carbon sources compared to those that evolved on glucose. These results provide a novel systematic view of the mechanisms underlying microbial adaptation to growth on a gluconeogenic substrate.

Published ahead of print on 18 May 2007.

Present address: Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA 23284-3028.