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A unifying paradigm for naphthoquinone-based meroterpenoid (bio)synthesis

TitleA unifying paradigm for naphthoquinone-based meroterpenoid (bio)synthesis
Publication TypeJournal Article
Year of Publication2017
AuthorsMiles Z.D, Diethelm S., Pepper H.P, Huang D.M, George J.H, Moore BS
JournalNature Chemistry
Date Published2017/12
Type of ArticleArticle
ISBN Number1755-4330
Accession NumberWOS:000416026200015
Keywordsactinomycete; antibiotics napyradiomycins; biomimetic; biosynthesis; cyclization; diverse; merochlorins; natural-products; rearrangement; synthesis; vanadium-bromoperoxidase

Bacterial meroterpenoids constitute an important class of natural products with diverse biological properties and therapeutic potential. The biosynthetic logic for their production is unknown and defies explanation via classical biochemical paradigms. A large subgroup of naphthoquinone-based meroterpenoids exhibits a substitution pattern of the polyketide-derived aromatic core that seemingly contradicts the established reactivity pattern of polyketide phenol nucleophiles and terpene diphosphate electrophiles. We report the discovery of a hitherto unprecedented enzyme-promoted alpha-hydroxyketone rearrangement catalysed by vanadium-dependent haloperoxidases to account for these discrepancies in the merochlorin and napyradiomycin class of meroterpenoid antibiotics, and we demonstrate that the alpha-hydroxyketone rearrangement is potentially a conserved biosynthetic reaction in this molecular class. The biosynthetic alpha-hydroxyketone rearrangement was applied in a concise total synthesis of naphthomevalin, a prominent member of the napyradiomycin meroterpenes, and sheds further light on the mechanism of this unifying enzymatic transformation.

Short TitleNat. Chem.
Student Publication: 
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