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How to Recruit a Promiscuous Enzyme to Serve a New Function
Shelley D Copley1, Matilda S Newton1, Karl A Widney1
1Department of Molecular, Cellular and Developmental Biology and the Cooperative Institute for Research in Environmental Sciences, Campus Box 347, University of Colorado Boulder, Boulder, Colorado 80309, United States.
Biochemistry
|June 21, 2022
Summary
Enzymes with promiscuous activities offer a vast catalytic potential. However, most are too inefficient to impact fitness, though mutations can enhance their utility, especially in large populations.
Area of Science:
- Biochemistry
- Evolutionary Biology
- Enzymology
Background:
- Enzymes possess promiscuous activities, catalyzing reactions beyond their native function.
- Gene duplication and divergence can evolve these promiscuous activities into specialized enzymes.
- Organisms harbor numerous promiscuous enzyme activities, representing a significant, yet often inaccessible, catalytic reservoir.
Purpose of the Study:
- To assess the catalytic efficiency of promiscuous enzyme activities.
- To estimate the impact of these activities on organismal fitness.
- To explore mechanisms by which promiscuous activities can be enhanced and recruited for new functions.
Main Methods:
- Compilation of kinetic parameters (kcat/KM) for promiscuous reactions from 108 enzymes.
- Estimation of metabolic fluxes in E. coli to contextualize enzyme efficiency.
- Analysis of mutation-driven mechanisms for enhancing promiscuous activity levels.
Main Results:
- The median catalytic efficiency (kcat/KM) for promiscuous reactions was found to be a modest 31 M^-1 s^-1.
- Many promiscuous activities are likely too inefficient to significantly influence fitness based on metabolic pathway fluxes.
- Mutations affecting enzyme expression, catalytic efficiency, or substrate/regulator concentrations can enhance insufficient promiscuous activities.
Conclusions:
- While many promiscuous enzyme activities are inefficient, they represent a latent resource for evolutionary innovation.
- Mutations, particularly within large populations, can facilitate the recruitment and optimization of these promiscuous activities for new adaptive roles.
- Understanding promiscuous enzyme potential is key to comprehending enzyme evolution and adaptation.
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