Halogenated natural products play important roles as antibiotics, antifungals,
and antitumor agents. The process of halogenation involves the replacement of a
hydrogen with a halide (such as chloride or bromide), and is a challenging task
for a synthetic chemist. However, the iron-containing enzymes in the
haloperoxidase and halogenase families readily catalyze these reactions. It is
thought that when this reaction occurs, the iron in the enzyme is at a
high-valent Fe(IV) state, and that this species is responsible for removing a
hydrogen atom (called an abstraction) from the substrate, creating a substrate
radical, and that a halogen radical is subsequently transferred to the
substrate to complete the halogenation reaction. Recently, Pamela Riggs-Gelasco
and co-workers used x-ray absorption spectroscopy at SSRL's Beam Line 7-3 to
obtain unique structural insights into this enzymatic intermediate in the
halogenase CytC3. The extended x-ray absorption fine structure (EXAFS) data
showed the presence of a short Fe-O bond and a Fe-Br interaction, clearly
identifying a Br-Fe(IV)=O2- unit and confirming a key component in
the enzymatic mechanism.
Galonic Fujimori, D., Barr, E. W., Matthews, M.L., Koch, G. L., Yonce, J. R.*,
Walsh, C. T., Bollinger, J. M., Jr., Krebs, C., Riggs-Gelasco, P. J.
"Spectroscopic Evidence for a High-Spin Br-Fe(IV)-Oxo Intermediate in the
a-Ketoglutarate-Dependent Halogenase CytC3 from
Streptomyces", 2007, J. Am.
Chem. Soc., 129, 13408-13409.
To learn more about this research see the full scientific highlight at:
http://www-
ssrl.slac.stanford.edu/research/highlights_archive/halogenasecytc3.html
