Open an undergraduate biochemistry textbook and you will learn that enzymes are highly efficient and specific in catalyzing chemical reactions in living organisms, and that they evolved to this state from their sloppy and promiscuous ancestors to allow cells to grow more efficiently. This fundamental paradigm is being challenged in a new study by bioengineers at the University of California, San Diego, who reported in the journal Science what a few enzymologists have suspected for years: many enzymes are still pretty sloppy and promiscuous, catalyzing multiple chemical reactions in living cells, for reasons that were previously not well understood.
In this study, the research team, led by Bernhard Palsson, Galetti Professor of Bioengineering at the UC San Diego Jacobs School of Engineering, brought together decades of work on the behavior of individual enzymes to produce a genome-scale model of E. coli metabolism and report that at least 37 percent of its enzymes catalyze multiple metabolic reactions that occur in an actively growing cell.
Weve been able to stitch all of the enzymes together into one giant model, giving us a holistic view of what has been driving the evolution of enzymes and found that it isnt quite what weve thought it to be, said Palsson.
When organisms evolve, it is the genes or proteins that change. Therefore, gene and protein evolution has classically been studied one gene at a time. However in this work, Palsson and his colleagues, introduce an important paradigm shift by demonstrating that the evolution of individual proteins and enzymes is influenced by the function of all of the other enzymes in an organism, and how they all work together to support the growth rate of the cell.
Using a whole-cell model of metabolism, the research team found that the more essential an enzyme is to the growth of the cell, the more efficient it needs to be; meanwhile, enzymes that only weakly contribute to cell growth can
|Contact: Catherine Hockmuth|
University of California - San Diego