title: Production of Stealthin C Involves an S-N-Type Smiles Rearrangement.
abstract: 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.
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Gloria J
authors.initials: GJ
authors.lastname: Hong
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Wilson
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Emily P
authors.identifier: 0000-0001-5985-5714
authors.initials: EP
authors.lastname: Balskus
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism
chemical_list: D001688:Biological Products; D006576:Heterocyclic Compounds, 4 or More Rings; C000627231:seongomycin; C000627230:stealthin C; D006899:Mixed Function Oxygenases