화학공학소재연구정보센터
Journal of the American Chemical Society, Vol.140, No.48, 16661-16668, 2018
Radical S-Adenosyl-L-methionine Tryptophan Lyase (NosL): How the Protein Controls the Carboxyl Radical center dot CO2- Migration
The radical S-adenosyl-L-methionine tryptophan lyase uses radical-based chemistry to convert L-tryptophan into 3-methyl-2-indolic acid, a fragment in the biosynthesis of the thiopeptide antibiotic nosiheptide. This complex reaction involves several successive steps corresponding to (i) the activation by a specific hydrogen-atom abstraction, (ii) an unprecedented center dot CO2- radical migration, (iii) a cyanide fragment release, and (iv) the termination of the radical-based reaction. In vitro study of this reaction is made more difficult because the enzyme produces a significant amount of a shunt product instead of the natural product. Here, using a combination of X-ray crystallography, electron paramagnetic resonance spectroscopy, and quantum and hybrid quantum mechanical/molecular mechanical calculations, we have deciphered the fine mechanism of the key center dot CO2- radical migration, highlighting how the preorganized active site of the protein tightly controls this reaction.