Methanobactin Redux

USING NUCLEAR magnetic resonance spectroscopy and other methods, chemists have detected an error in, and have revised, the published structure of methanobactin, a copper-binding peptide used by methane-metabolizing bacteria (J. Am. Chem. Soc., DOI: 10.1021/ja804747d). The new structure represents a significant finding because researchers are studying the methanotrophic bacteria that produce the peptide for their ability to remove methane, a greenhouse gas, from the atmosphere.

The bacteria use methanobactin to scavenge copper for use by particulate methane mono-oxygenase (pMMO), the enzyme that catalyzes the oxidation of methane to methanol. The first report of the complete structure for methanobactin described it as a peptide with seven amino acids and two hydroxyimidazolate rings (C&EN, Sept. 13, 2004, page 24).

Now, a team led by Warren H. Gallagher of the University of Wisconsin, Eau Claire, reports that methanobactin contains oxazolone rings instead of hydroxyimidazolates and a 3-methylbutanoyl instead of an isopropyl ester.

David W. Graham, a professor of environmental engineering at the University of Newcastle, in England, and the leader of the team that originally reported the structure of methanobactin, says, "I had never been completely confident that we had the structure 100% correct because some of the elements were so unusual."

Gallagher and coworkers figured out something was amiss when they started looking at methanobactin with NMR spectroscopy. "The NMR pattern for one part of the molecule didn't match the published structure at all," Gallagher says. Simply swapping an isobutyl group for the isopropyl group would throw off the molecular weight, so the team started digging into the rest of the molecule for other possible errors. They realized that switching one nitrogen in each of the two hydroxyimidazolate rings to oxygen would balance the mass change.

Methanobactin "is the founding member of what I think is going to be a large and diverse family of copper chelators, so it is critical that we know its exact structure," says Amy C. Rosenzweig, a biochemistry professor at Northwestern University. "The newly reported oxazolone rings provide some clues into methanobactin biosynthesis."

The revisions suggest possible pathways for synthesizing methanobactin. "The oxazolones we're proposing are closely related to oxazolines," Gallagher says. "The chemistry of how they might be formed from amino acids is much more straightforward."