Network-level architecture and the evolutionary potential of underground metabolism
Abstract
Understanding how new metabolic pathways emerge is one of the key issues in evolutionary and systems biology. The prevailing paradigm is that evolution capitalizes on the weak side activities of preexisting enzymes (i.e. underground reactions). However, the extent to which underground reactions provide novelties in the context of the entire cellular system has remained unexplored. In this study, we present a comprehensive computational model of the underground metabolism of Escherichia coli. Together with a high-throughput experimental survey across hundreds of nutrient environments we predicted and confirmed new functional states of metabolism in which underground reactions allow growth when their activity is increased. Our approach has important implications for biotechnological and medical applications, such as understanding gain-of-function mutations in tumor development.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- August 2014
- DOI:
- 10.1073/pnas.1406102111
- Bibcode:
- 2014PNAS..11111762N