Understanding the Number of Different Substrates Used by Enzymes

Enzyme “promiscuity” and “monogamy” play a significant role in myriad biochemical reactions.

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Image courtesy of “Constraint-based Modeling: Part I” by Bernard O. Palsson. http://gcrg.ucsd.edu/HomeExternal link

Graphical representation of enzyme network necessary for metabolism.

The Science

Enzymes with very specialized function maintain a higher flux, or processing rate, and require more regulation of their activities.

The Impact

These new results offer a means of translating genomic information into enzyme functional capabilities with particular relevance for microbes involved in biofuel production.


In biology, some enzymes are highly specialized and catalyze specific reactions with few or only one substrate while other enzymes are promiscuous and can catalyze reactions using a variety of substrates. This phenomenon has also been observed experimentally for microbes involved in bioenergy related processes. However, we don’t understand why, within an organism, some enzymes are highly specialized while others remain generalists. Recently Nam and co-workers have addressed this question using whole genome metabolic reconstructions and analysis, including dynamical simulations of environmental changes to understand microbial responses. The higher flux and higher regulation allows enzymes with very specialized functions to be more responsive and adaptive to environmental surroundings and changes then their less specialized counterparts. This work also illustrates that understanding environmental cellular physiology is greatly enhanced when using a systems biology approach rather than approaches that are focused on single enzymes simulations.


Dr. Nathan Lewis
Harvard University


DOE Office of Science Biological and Environmental Research (BER) program


Hojung Nam, Nathan E. Lewis, Joshua A. Lerman, Dae-Hee Lee, Roger L. Chang, Donghyuk Kim, Bernhard O. Palsson , “Network Context and Selection in the Evolution to Enzyme Specificity”, Science 10.1126/science.1216861 (2012).

Highlight Categories

Program: BER, BSSD

Performer/Facility: Industry

Last modified: 1/3/2016 12:03:44 PM