Enzyme promiscuity shapes adaptation to novel growth substrates.

Autor: Guzmán GI; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA., Sandberg TE; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA., LaCroix RA; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA., Nyerges Á; Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary., Papp H; Virological Research Group, Szentágothai Research Centre University of Pécs, Pécs, Hungary., de Raad M; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory Berkeley, Berkeley, CA, USA., King ZA; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA., Hefner Y; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA., Northen TR; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory Berkeley, Berkeley, CA, USA., Notebaart RA; Laboratory of Food Microbiology, Wageningen University and Research, Wageningen, The Netherlands., Pál C; Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary., Palsson BO; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA., Papp B; Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary., Feist AM; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA afeist@ucsd.edu.; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Jazyk: angličtina
Zdroj: Molecular systems biology [Mol Syst Biol] 2019 Apr 08; Vol. 15 (4), pp. e8462. Date of Electronic Publication: 2019 Apr 08.
DOI: 10.15252/msb.20188462
Abstrakt: Evidence suggests that novel enzyme functions evolved from low-level promiscuous activities in ancestral enzymes. Yet, the evolutionary dynamics and physiological mechanisms of how such side activities contribute to systems-level adaptations are not well characterized. Furthermore, it remains untested whether knowledge of an organism's promiscuous reaction set, or underground metabolism, can aid in forecasting the genetic basis of metabolic adaptations. Here, we employ a computational model of underground metabolism and laboratory evolution experiments to examine the role of enzyme promiscuity in the acquisition and optimization of growth on predicted non-native substrates in Escherichia coli K-12 MG1655. After as few as approximately 20 generations, evolved populations repeatedly acquired the capacity to grow on five predicted non-native substrates-D-lyxose, D-2-deoxyribose, D-arabinose, m-tartrate, and monomethyl succinate. Altered promiscuous activities were shown to be directly involved in establishing high-efficiency pathways. Structural mutations shifted enzyme substrate turnover rates toward the new substrate while retaining a preference for the primary substrate. Finally, genes underlying the phenotypic innovations were accurately predicted by genome-scale model simulations of metabolism with enzyme promiscuity.
(© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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