Details

Autor(en) / Beteiligte

• Parkinson, Elizabeth I.
• Lakkis, Hani G.
• Alwali, Amir A.
• Metcalf, Mary Elizabeth M.
• Modi, Ramya
• Metcalf, William W.

Titel

An Unusual Oxidative Rearrangement Catalyzed by a Divergent Member of the 2‐Oxoglutarate‐Dependent Dioxygenase Superfamily during Biosynthesis of Dehydrofosmidomycin

Ist Teil von

• Angewandte Chemie International Edition, 2022-07, Vol.61 (30), p.e202206173-n/a

Auflage

International ed. in English

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The biosynthesis of the natural product dehydrofosmidomycin involves an unusual transformation in which 2‐(trimethylamino)ethylphosphonate is rearranged, desaturated and demethylated by the enzyme DfmD, a divergent member of the 2‐oxoglutarate‐dependent dioxygenase superfamily. Although other members of this enzyme family catalyze superficially similar transformations, the combination of all three reactions in a single enzyme has not previously been observed. By characterizing the products of in vitro reactions with labeled and unlabeled substrates, we show that DfmD performs this transformation in two steps, with the first involving desaturation of the substrate to form 2‐(trimethylamino)vinylphosphonate, and the second involving rearrangement and demethylation to form methyldehydrofosmidomycin. These data reveal significant differences from the desaturation and rearrangement reactions catalyzed by other family members. DfmD is a highly divergent member of the 2‐oxoglutarate‐dependent dioxygenase superfamily that catalyzes desaturation, rearrangement and demethylation of its substrate. In vitro biochemical studies and homology modeling suggest that these transformations occur via novel chemistry.