After years of wondering how organisms managed to create medically valuable natural products, like antibiotics and anti-fungal agents, chemists have discovered the surprisingly simple secret by shining x-ray light on the problem. MIT and Harvard researchers used crystallography beam lines at the Stanford Synchrotron Radiation Laboratory and the Advanced Light Source in Berkeley for their research.

They determined the atomic structure of an iron-dependent halogenase, the enzyme SyrB2, from the plant pathogen Pseudomonas syringae. This enzyme catalyzes the chlorination of threonine during biosynthesis of the anti-fungal agent syringomycin, a natural-product antibiotic. This provides one example of how an enzyme can coax a reaction to generate medically valuable halogenated natural products. The products include antibiotics, anti-tumor agents and fungicides, and they are challenging to synthesize in a laboratory. The crystallography study revealed in this case how the specific structure at the iron-containing active site of the enzyme (the site responsible for the chemical reaction) provides information that can help in understanding how the chemical process takes place.

The structure revealed a novel coordination for iron that contains a chloride ion together with two histidine amino acids, a deviation from the way an iron atom is normally held in an enzyme's active site of this kind in that it does not contain a carboxylate-containing amino acid. The position of the surrounding amino acids indicate that the structure has more room at the active site, enough space for the chloride to enter and bind to the iron as part of the chemical reaction.

"Now that we have the enzyme's structure and figured out how it works, it makes sense. But it's not what we would have predicted," said Catherine Drennan of MIT. "Things are usually not this simple, but there's an elegant beauty in this simplicity," one that might help chemistry labs gain the enzyme's capabilities.

To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/ research/highlights_archive/SyrB2.html

L. C. Blasiak, F. H. Vaillancourt, C. T. Walsh and C. L. Drennan, "Crystal Structure of the Non-haem Iron Halogenase SyrB2 in Syringomycin Biosynthesis", Nature 440, 368 (2006)