An Unusual Oxidative Rearrangement Catalyzed by a Divergent Member of the 2-Oxoglutarate-Dependent Dioxygenase Superfamily during Biosynthesis of Dehydrofosmidomycin.
An Unusual Oxidative Rearrangement Catalyzed by a Divergent Member of the 2-Oxoglutarate-Dependent Dioxygenase Superfamily during Biosynthesis of Dehydrofosmidomycin.
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DOI：
10.1002/anie.202206173
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发表时间：
2022-07-25
影响因子：
16.6
通讯作者：
Metcalf, William W.
中科院分区：
文献类型：
--
作者：
Parkinson, Elizabeth, I;Lakkis, Hani G.;Alwali, Amir A.;Metcalf, Mary Elizabeth M.;Modi, Ramya;Metcalf, William W.
天然产物脱氢磷霉素的生物合成涉及一个不寻常的转化过程，在这个过程中，2-(三甲氨基)乙基膦酸酯被DfmD酶重排、去饱和和去甲基化，DfmD是依赖2-氧代戊二酸的双加氧酶超家族中的一个不同的成员。虽然这个酶家族的其他成员催化表面上类似的转换，但以前从未观察到在一个酶中所有三个反应的组合。通过对标记底物和未标记底物的体外反应产物的表征，我们发现DfmD进行这种转化分两步进行，第一步是底物脱饱和生成2-(三甲氨基)乙烯基膦酸酯，第二步是重排和脱甲基化生成甲基脱氢磷霉素。这些数据揭示了与其他家族成员催化的去饱和和重排反应的显著差异。DfmD是依赖2-氧戊二酸的双加氧酶超家族中的一个高度分化的成员，它催化底物的去饱和、重排和去甲基化。体外生化研究和同源建模表明，这些转变是通过新的化学作用发生的。
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.
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DOI：
10.1002/chem.201503761
发表时间：
2016-01-22
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Kamps JJ;Khan A;Choi H;Lesniak RK;Brem J;Rydzik AM;McDonough MA;Schofield CJ;Claridge TD;Mecinović J
通讯作者：
Mecinović J
海洋微生物合成甲基膦酸：有氧海洋中甲烷的来源。
DOI：
10.1126/science.1219875
发表时间：
2012-08-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Metcalf WW;Griffin BM;Cicchillo RM;Gao J;Janga SC;Cooke HA;Circello BT;Evans BS;Martens-Habbena W;Stahl DA;van der Donk WA
通讯作者：
van der Donk WA
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
2.9
作者：
Luo, LS;Pappalardi, MB;Hausinger, RP
通讯作者：
Hausinger, RP