‘Promiscuous’ enzymes can compensate for disabled genes

WASHINGTON — When bacteria lose genes needed to make enzymes for important chemical reactions, defeat isn’t inevitable. Sometimes other enzymes will take on new roles to patch together a work-around chain of reactions that does the job, biologist Shelley Copley reported August 4 at the 2nd American Society for Microbiology Conference on Experimental Microbial Evolution.

Bacteria that can adapt in this way are more likely to survive when living conditions change, passing along these new tricks to their descendants. So studying these biochemical gymnastics is helping scientists to understand how evolution works on a molecular level.

Working with different strains of Escherichia coli bacteria, Copley and colleagues deleted genes responsible for making crucial enzymes. The team then watched the microbes replicate for many generations to see how they worked around those limitations.

Most enzymes are highly specialized: They only work well to speed up one type of reaction, the way a key fits only one lock. But some enzymes are more like master keys — they can boost multiple reactions, though they tend to specialize in one. These so-called “promiscuous” enzymes can switch away from their specialty if conditions change.

Copley’s team found that new enzymes would sub in to replace the missing ones. For instance, E. coli missing an enzyme needed to make vitamin B6 synthesized the vitamin using a different set of enzymes. But surprisingly, the promiscuous enzymes didn’t end up directly triggering the same reaction as the enzymes they replaced. Instead, the replacement enzymes cobbled together a different (often longer) work-around series of reactions that ultimately achieved the same function.

“We were rerouting metabolism,” said Copley, of the University of Colorado Boulder.

By modifying the bacteria’s genes and forcing the microbes to survive with a more limited chemical toolkit, Copley’s work gives a more detailed look at the biochemistry underlying evolution, says biologist Gavin Sherlock of Stanford University, who was not involved in the research.

Betul Kacar, a synthetic biologist at Harvard University, says promiscuity could also be a window into the past, giving hints about enzymes’ previous roles earlier in evolutionary history. The role that an enzyme jumps in to play in a pinch could have once been its main job. “Trying to understand how novel pathways arise, what kind of mechanistic underlying forces shape those trajectories, is quite essential,” she says.

Bacteria can piece together all sorts of alternative routes in response to missing enzymes, depending on specific environmental conditions, Copley said. The ones that are most successful are more efficient —they have fewer steps, or they yield more of the desired reaction product.