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Network-level architecture and the evolutionary potential of underground metabolism

2014; National Academy of Sciences; Volume: 111; Issue: 32 Linguagem: Inglês

10.1073/pnas.1406102111

1091-6490

Richard A. Notebaart, Balázs Szappanos, Bálint Kintses, Ferenc Pál, Ádám Györkei, Balázs Bogos, Viktória Lázár, Réka Spohn, Bálint Csörgő, Allon Wagner, Eytan Ruppin, Csaba Pál, Balázs Papp,

Bioinformatics and Genomic Networks

Significance 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.