Why are some enzymes so promiscuous?

Enzymes are often thought to be specific, catalysing only one reaction in a cell (left), but some more promiscuous enzymes have many functions and catalyse many reactions in a cell. Image: Courtesy of Systems Biology Research Group, UC San Diego, Jacobs School of Engineering

Enzymes are meant to be specific, right?

Well, that’s the theory — enzymes are supposed to have evolved from more sloppy and promiscuous ancestors to catalyse specific chemical reactions in living organisms. Some enzymologists, however, have suspected for a while that many of them are still sloppy and promiscuous.

This suspicion has now been confirmed by a team of bioengineers, who brought together extensive research on the behaviour of enzymes to create a produce a genome-scale model of E. coli metabolism. They reported in a study published in Science that 37 per cent of its enzymes are catalysing multiple reactions inside active cells. That’s a lot of promiscuous enzymes.

“We’ve 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 isn’t quite what we’ve thought it to be,” says professor Bernhard Palsson from the University of California — San Diego, who led the study. When organisms evolve, its genes or proteins — each of which have specific functions in a cell — change and influence the evolution of the other genes and proteins.

In the case of the pickier enzymes, Palsson and his colleagues have shown that their evolution is influenced by the functions of the other enzymes and how they all work together in supporting a cell’s growth rate. They found that the enzymes that play an important role in cell growth need to be efficient, while those that aren’t strong contributors tend to be sloppier.

There appear to be three reasons for this:

1. Enzymes that are used more extensively in the cell need to be more efficient to avoid waste and therefore only catalyse one reaction.

2. If they are catalysing reactions necessary for cell growth and survival, they tend to be more specific to avoid interference.

3. The organisms need to carefully control some reactions to avoid wasting energy, making these enzymes more specific makes them easier to control

So if an enzyme is important, it’s probably going to become picky. However, this isn’t to say that the promiscuous enzymes aren’t still used by the growing cells — the researchers found that this sloppiness isn’t detrimental to growth. “They are much less sensitive to changes in the environment and not as necessary for efficient cell growth,” says Dr Nathan Lewis from Harvard Medical School in the US.


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