ASR - Enzymatic Chlorination of Tryptophan

Naturally occurring halogenated organic compounds are rare in most biological systems. However, these are commonly used same in many marine organisms, fungi, and bacteria; and several thousand different naturally occurring halogenated compounds have been isolated and identified from these species. Although rare, there are a few examples of biological halogenated compounds produced by humans; one of them is tetraiodothyronine, an endocrine hormone. 

 Halogenase enzymes use metal centers to accomplish halogen insertion (usually iron or vanadium).  The basic strategy of these enzymes is to use the metal center to oxidize a halide anion to a cation species (a two-electron oxidation) or radical species (a one-electron oxidation) so that the halogen cations can react with alkenes and benzene rings and the radicals attach to the unactivated alkyl group.

X^- → X⁺ + 2e^-

X^- → X• + e^-

However,  a metal-free halogenase has been discovered. This halogenase uses only FADH₂ to introduce a chlorine to the aromatic ring of tryptophan. The reaction mechanism relies on the generation of flavin hydroperoxide from FADH₂ and molecular oxygen, just like the two flavin-dependant monooxygenases discussed earlier.  Chloride ion attacks the hydroperoxide, generating ClOH, or hypochlorous acid.

After traveling through a 10 angstrom long tunnel inside the enzyme, the HOCl intermediate comes into contact with C₇ of tryptophan, and reacts as the electrophilic molecule in an electrophilic aromatic substitution.

 Tryptophan :
IUPAC: (2S)-2-amino-3-(1H-indol-3-yl)propanoic acid
MW: 204.225g/mol
Formula: C11H12N2O2

7-chlorotryptophan :
IUPAC: 7-chloro-L-tryptophan
MW: 238.67
Formula: C11H11ClN2O2

References:

Chlorination of tryptophan http://chemwiki.ucdavis.edu/Organic_Chemistry/Organic_Chemistry_With_a_Biological_Emphasis/. (Accessed on March 11, 2014)

http://www.chemicalbook.com/