Megaenzymes — proteins that play a big part in creating antibiotics — are constantly moving to create compounds, so it’s difficult to take pictures of them. But in new research published in Nature, researchers describe a way to take live snapshots of medicine-making enzymes as they’re working their magic. Here’s what study author and McGill University biochemist Martin Schmeing said about the new findings.
How do the proteins that make up megaenzymes work to build antibiotics?
It’s very much like a car assembly line where every station adds a new part of a car. [Parts of the proteins] work together to add one new part of the product, often antibiotics. … These enzymes naturally occur within bacteria to produce compounds that kill their competitors, and that’s very useful because if we can isolate these compounds, we can use them to make antibiotics.
And why is it hard to see how those megaenzymes are working?
They have moving parts — they pick something up, move it to a new site, add something, move it to the next site. … So if the enzyme’s job was to dance the YMCA, we want all our enzymes to be first in the Y so you can see what it looks like as they Y, and then you want them to stop all at the M, and so on.
What did your research do to make that possible?
We have to trap the enzyme in a single state, so we give it a chemical that’s a lot like the one it would use to put together antibiotics, but has something a little wrong with it. The enzyme can grab the chemical but we can make it not bring it to the next site. … If we can mess around with the enzyme, we can maybe get it to make a new, modified antibiotics. The dream is to take the way these proteins make the compounds and be able to bioengineer them ourselves.