Enzyme promiscuity shapes adaptation to novel growth substrates

Guzmán, Gabriela I.; Sandberg, Troy E.; LaCroix, Ryan A.; Nyerges, Ákos; Papp, Henrietta; de Raad, Markus; King, Zachary A.; Hefner, Ying; Northen, Trent R.; Notebaart, Richard A.; Pál, Csaba; Palsson, Bernhard O.; Papp, Balázs; Feist, Adam M.

doi:10.15252/msb.20188462

Title: Enzyme promiscuity shapes adaptation to novel growth substrates

Journal Article · Mon Apr 08 00:00:00 EDT 2019 · Molecular Systems Biology

DOI:https://doi.org/10.15252/msb.20188462· OSTI ID:1546852

Guzmán, Gabriela I. ^[1];

^[1]; LaCroix, Ryan A. ^[1];

^[2]; Papp, Henrietta ^[3]; de Raad, Markus ^[4]; King, Zachary A. ^[1]; Hefner, Ying ^[1]; Northen, Trent R. ^[4]; Notebaart, Richard A. ^[5]; Pál, Csaba ^[2];

^[6]; Papp, Balázs ^[2];

^[7]

Department of Bioengineering University of California, San Diego La Jolla CA USA
Synthetic and Systems Biology Unit Institute of Biochemistry Biological Research Centre of the Hungarian Academy of Sciences Szeged Hungary
Virological Research Group Szentágothai Research Centre University of Pécs Pécs Hungary
Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory Berkeley Berkeley CA USA
Laboratory of Food Microbiology Wageningen University and Research Wageningen The Netherlands
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
Department of Bioengineering University of California, San Diego La Jolla CA USA, Novo Nordisk Foundation Center for Biosustainability Technical University of Denmark Lyngby Denmark

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 MG 1655. 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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); • Novo Nordisk Fonden (NNF). Grant Number: NNF10CC1016517; EC|H2020|H2020 Priority Excellent Science | H2020 European Research Council ERC); “Lendület” Programme of the Hungarian Academy of Sciences; The Wellcome Trust; EVOMER; National Research, Development and Innovation Office, Hungary

Grant/Contract Number:: DE‐AC02‐05CH11231; AC02-05CH11231; NNF10CC1016517; H2020‐ERC‐2014‐CoG; GINOP‐2.3.2‐15‐2016‐00014; KH125616

OSTI ID:: 1546852

Alternate ID(s):: OSTI ID: 1546857; OSTI ID: 1627938

Journal Information:: Molecular Systems Biology, Journal Name: Molecular Systems Biology Vol. 15 Journal Issue: 4; ISSN 1744-4292

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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Cited by: 38 works

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