Enzyme promiscuity shapes adaptation to novel growth substrates

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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.
Original languageEnglish
Article numbere8462
JournalMolecular Systems Biology
Volume15
Issue number4
ISSN1744-4292
DOIs
Publication statusPublished - 2019

Keywords

  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)
  • Agricultural and Biological Sciences (all)
  • Applied Mathematics
  • adaptive evolution
  • enzyme promiscuity
  • genome‐scale modeling
  • systems biology

Cite this

Guzmán, G. I., Sandberg, T. E., LaCroix, R. A., Nyerges, Á., Papp, H., de Raad, M., ... Feist, A. M. (2019). Enzyme promiscuity shapes adaptation to novel growth substrates. Molecular Systems Biology, 15(4), [e8462]. https://doi.org/10.15252/msb.20188462
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. / Enzyme promiscuity shapes adaptation to novel growth substrates. In: Molecular Systems Biology. 2019 ; Vol. 15, No. 4.
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title = "Enzyme promiscuity shapes adaptation to novel growth substrates",
abstract = "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.",
keywords = "Biochemistry, Genetics and Molecular Biology (all), Immunology and Microbiology (all), Agricultural and Biological Sciences (all), Applied Mathematics, adaptive evolution, enzyme promiscuity, genome‐scale modeling, systems biology",
author = "Guzm{\'a}n, {Gabriela I.} and Sandberg, {Troy E.} and LaCroix, {Ryan A.} and {\'A}kos Nyerges and Henrietta Papp and {de Raad}, Markus and King, {Zachary A.} and Ying Hefner and Northen, {Trent R.} and Notebaart, {Richard A.} and Csaba P{\'a}l and Palsson, {Bernhard O.} and Bal{\'a}zs Papp and Feist, {Adam M.}",
year = "2019",
doi = "10.15252/msb.20188462",
language = "English",
volume = "15",
journal = "Molecular Systems Biology",
issn = "1744-4292",
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Guzmán, GI, Sandberg, TE, LaCroix, RA, Nyerges, Á, Papp, H, de Raad, M, King, ZA, Hefner, Y, Northen, TR, Notebaart, RA, Pál, C, Palsson, BO, Papp, B & Feist, AM 2019, 'Enzyme promiscuity shapes adaptation to novel growth substrates', Molecular Systems Biology, vol. 15, no. 4, e8462. https://doi.org/10.15252/msb.20188462

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.

In: Molecular Systems Biology, Vol. 15, No. 4, e8462, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Enzyme promiscuity shapes adaptation to novel growth substrates

AU - Guzmán, Gabriela I.

AU - Sandberg, Troy E.

AU - LaCroix, Ryan A.

AU - Nyerges, Ákos

AU - Papp, Henrietta

AU - de Raad, Markus

AU - King, Zachary A.

AU - Hefner, Ying

AU - Northen, Trent R.

AU - Notebaart, Richard A.

AU - Pál, Csaba

AU - Palsson, Bernhard O.

AU - Papp, Balázs

AU - Feist, Adam M.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Biochemistry, Genetics and Molecular Biology (all)

KW - Immunology and Microbiology (all)

KW - Agricultural and Biological Sciences (all)

KW - Applied Mathematics

KW - adaptive evolution

KW - enzyme promiscuity

KW - genome‐scale modeling

KW - systems biology

U2 - 10.15252/msb.20188462

DO - 10.15252/msb.20188462

M3 - Journal article

VL - 15

JO - Molecular Systems Biology

JF - Molecular Systems Biology

SN - 1744-4292

IS - 4

M1 - e8462

ER -

Guzmán GI, Sandberg TE, LaCroix RA, Nyerges Á, Papp H, de Raad M et al. Enzyme promiscuity shapes adaptation to novel growth substrates. Molecular Systems Biology. 2019;15(4). e8462. https://doi.org/10.15252/msb.20188462