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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.

SUBMITTER: Notebaart RA

PROVIDER: S-EPMC4136603 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Network-level architecture and the evolutionary potential of underground metabolism.

Notebaart Richard A RA Szappanos Balázs B Kintses Bálint B Pál Ferenc F Györkei Ádám Á Bogos Balázs B Lázár Viktória V Spohn Réka R Csörgő Bálint B Wagner Allon A Ruppin Eytan E Pál Csaba C Papp Balázs B

Proceedings of the National Academy of Sciences of the United States of America 20140728 32

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 computati ...[more]

PMID: 25071190

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Network-level architecture and the evolutionary potential of underground metabolism.

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Network-level architecture and the evolutionary potential of underground metabolism.

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