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Production of Stealthin C Involves an S–N-Type Smiles Rearrangement
- Wang, Peng, Hong, Gloria J., Wilson, Matthew R., Balskus, Emily P.
- Journal of the American Chemical Society 2017 v.139 no.8 pp. 2864-2867
- acetylcysteine, chemistry, cysteine, metabolites
- The kinamycin family of aromatic polyketide natural products contains an atypical angucycline ring system substituted with a diazo group. The enzymatic chemistry involved in constructing both of these structural features has been largely unexplored. Here we report the in vivo and in vitro production of seongomycin, a shunt product from this pathway, and stealthin C, a proposed biosynthetic precursor to the kinamycins. We show that a single enzyme, the flavin-dependent monooxygenase AlpJ, can generate these metabolites from N-acetyl-l-cysteine and l-cysteine, respectively, and that the synthesis of stealthin C likely proceeds via a nonenzymatic S–N-type Smiles rearrangement. This unexpected route to stealthin C reveals a distinct approach to install aromatic amino groups in metabolites and raises questions about the intermediacy of this species in kinamycin production.