Diradical intermediate within the context of tryptophan tryptophylquinone biosynthesis

Erik T. Yukl, Fange Liu, J. Krzystek, Sooim Shin, Lyndal M.R. Jensen, Victor L. Davidson, Carrie M. Wilmot, Aimin Liu

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Despite the importance of tryptophan (Trp) radicals in biology, very few radicals have been trapped and characterized in a physiologically meaningful context. Here we demonstrate that the diheme enzyme MauG uses Trp radical chemistry to catalyze formation of a Trp-derived tryptophan tryptophylquinone cofactor on its substrate protein, premethylamine dehydrogenase. The unusual sixelectron oxidation that results in tryptophan tryptophylquinone formation occurs in three discrete two-electron catalytic steps. Here the exact order of these oxidation steps in the processive six-electron biosynthetic reaction is determined, and reaction intermediates are structurally characterized. The intermediates observed in crystal structures are also verified in solution using mass spectrometry. Furthermore, an unprecedented Trp-derived diradical species on premethylamine dehydrogenase, which is an intermediate in the first two-electron step, is characterized using high-frequency and -field electron paramagnetic resonance spectroscopy and UV-visible absorbance spectroscopy. This work defines a uniquemechanism for radical-mediated catalysis of a protein substrate, and has broad implications in the areas of applied biocatalysis and understanding of oxidative protein modification during oxidative stress.

Original languageEnglish (US)
Pages (from-to)4569-4573
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Mar 19 2013


  • Cofactor biosynthesis
  • Electron transfer
  • Heme
  • Posttranslational modification
  • Tryptophan radical


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