From Curds, a New Way to Make Antibiotics
As antibiotic resistance spreads, researchers have stepped up the hunt for drugs that kill tough new strains of microbes. Now, LAS chemists have shown how an enzyme from cheese-making bacteria could help launch a powerful new class of antibiotics.
The bacterium Lactococcus lactis ferments milks into cheeses and makes molecules called lantibiotics that kill other bacteria. (One lantibiotic, nisin, has been used for 50 years as a food preservative.) To make new lantibiotics varied and powerful enough to stop dangerous pathogens, chemistry professors Willem van der Donk and Neil Kelleher, former graduate student Lili Xie, and their colleagues first cloned two genes that Lactococci use to make a lantibiotic called lacticin 481. One gene encodes a small string-shaped protein called a peptide; the second gene encodes an enzyme called LctM that turns the peptide into the microbe-killing drug.
In work published in Science in January, the chemists showed that LctM does that by first knocking four water molecules off the peptide, then tying three loops in it. The key experiments involved mixing shortened and otherwise altered versions of the peptide with LctM, isolating the resulting molecules, breaking them into pieces and determining the shapes and sizes of the pieces. The work also revealed that LctM can turn peptide variants into new types of lantibiotics, which "opens an avenue to engineer antibiotics," van der Donk says.
"It's important to renew our arsenal of compounds that combat pathogens," van der Donk concludes. "We will always need new antibiotics."