title: Network-level architecture and the evolutionary potential of underground metabolism.
abstract: A central unresolved issue in evolutionary biology is how metabolic innovations emerge. Low-level enzymatic side activities are frequent and can potentially be recruited for new biochemical functions. However, the role of such underground reactions in adaptation toward novel environments has remained largely unknown and out of reach of computational predictions, not least because these issues demand analyses at the level of the entire metabolic network. Here, we provide a comprehensive computational model of the underground metabolism in Escherichia coli. Most underground reactions are not isolated and 45% of them can be fully wired into the existing network and form novel pathways that produce key precursors for cell growth. This observation allowed us to conduct an integrated genome-wide in silico and experimental survey to characterize the evolutionary potential of E. coli to adapt to hundreds of nutrient conditions. We revealed that underground reactions allow growth in new environments when their activity is increased. We estimate that at least ∼20% of the underground reactions that can be connected to the existing network confer a fitness advantage under specific environments. Moreover, our results demonstrate that the genetic basis of evolutionary adaptations via underground metabolism is computationally predictable. The approach used here has potential for various application areas from bioengineering to medical genetics.
authors: Radboud Institute for Molecular Life Sciences, Centre for Bioinformatics and Systems Biology, Radboud University Medical Centre, 6525 GA, Nijmegen, The Netherlands; Richard.Notebaart@radboudumc.nl cpal@brc.hu pappb@brc.hu.
authors: Richard A
authors: RA
authors: Notebaart
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and.
authors: Balázs
authors: B
authors: Szappanos
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and.
authors: Bálint
authors: B
authors: Kintses
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and.
authors: Ferenc
authors: F
authors: Pál
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and.
authors: Ádám
authors: Á
authors: Györkei
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and.
authors: Balázs
authors: B
authors: Bogos
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and.
authors: Viktória
authors: V
authors: Lázár
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and.
authors: Réka
authors: R
authors: Spohn
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and.
authors: Bálint
authors: B
authors: Csörgő
authors: The Blavatnik School of Computer Science and.
authors: Allon
authors: A
authors: Wagner
authors: The Blavatnik School of Computer Science andSackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors: Eytan
authors: E
authors: Ruppin
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and Richard.Notebaart@radboudumc.nl cpal@brc.hu pappb@brc.hu.
authors: Csaba
authors: C
authors: Pál
authors: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, 6726, Szeged, Hungary; and Richard.Notebaart@radboudumc.nl cpal@brc.hu pappb@brc.hu.
authors: Balázs
authors: B
authors: Papp
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D005075:Biological Evolution; D003198:Computer Simulation; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D048168:Escherichia coli K12 / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D016680:Genome, Bacterial; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D010641:Phenotype
chemical_list: D004798:Enzymes; D029968:Escherichia coli Proteins
keywords: enzyme promiscuity; evolutionary innovation; molecular evolution; network evolution; phenotype microarray