How Gut Microbes Cut Choline Down To Size

Harvard University chemists have solved a 100-year mystery—how gut bacteria split the nutrient choline into trimethylamine and acetaldehyde (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1215689109). The microbes, it turns out, use an enzyme with a glycine-derived radical. This transformation, first reported in 1910, lies at the start of a metabolic pathway linked to diseases, including a rare ailment that causes fishy body odor. Smaranda Craciun and Emily P. Balskus searched the genome of a choline-degrading microbe for enzymes resembling those that break down ethanolamine, a molecule similar to choline. They turned up a set of genes, including one encoding a glycyl radical enzyme. The researchers show that the genes are involved in making fishy-smelling trimethylamine. Electron paramagnetic resonance spectroscopy on bacteria supplied with choline confirmed that a glycine-centered radical was present. The enzyme cleaves a C–N bond—so far, no other glycyl radical enzyme can do that, Balskus notes. With this information, scientists could someday analyze human gut microflora to determine whether they are a factor in developing trimethylamine-related diseases, says choline expert Steven H. Zeisel of the University of North Carolina, Chapel Hill.