Intracellular crowding defines the mode and sequence of substrate uptake by Escherichia coli and constrains its metabolic activity
The influence of the high intracellular concentration of macromolecules on cell physiology is increasingly appreciated, but its impact on system-level cellular functions remains poorly quantified. To assess its potential effect, here we develop a flux balance model of Escherichia coli cell metabolism that takes into account a systemslevel constraint for the concentration of enzymes catalyzing the various metabolic reactions in the crowded cytoplasm. We demonstrate that the model’s predictions for the relative maximum growth rate of wild-type and mutant E. coli cells in single substratelimited media, and the sequence and mode of substrate uptake and utilization from a complex medium are in good agreement with subsequent experimental observations. These results suggest that molecular crowding represents a bound on the achievable functional states of a metabolic network, and they indicate that models incorporating this constraint can systematically identify alterations in cellular metabolism activated in response to environmental change.
Q. K. Beg, A. Vazquez, J. Ernst, M. A. de Menezes, Z. Bar-Joseph, A.-L. Barabási, Z. N. Oltvai
July 31, 2007
Proceedings of the National Academy of Sciences 104, 31 (2007)
Kavitha Venkatesan, Jean-François Rual, Alexei Vazquez, Ulrich Stelzl, Irma Lemmens, Tomoko Hirozane-Kishikawa, Tong Hao, Martina Zenkner, Xiaofeng Xin, Kwang-Il Goh, Muhammed A Yildirim, Nicolas Simonis, Kathrin Heinzmann, Fana Gebreab, Julie M Sahalie, Sebiha Cevik, Christophe Simon, Anne-Sophie de Smet, Elizabeth Dann, Alex Smolyar, Arunachalam Vinayagam, Haiyuan Yu, David Szeto, Heather Borick, Amélie Dricot, Niels Klitgord, Ryan R Murray, Chenwei Lin, Maciej Lalowski, Jan Timm, Kirstin Rau, Charles Boone, Pascal Braun, Michael E Cusick, Frederick P Roth, David E Hill, Jan Tavernier, Erich E Wanker, Albert-László Barabási & Marc Vidal