Metagenomic ene-reductases for the bioreduction of sterically challenging enones.
Metagenomic ene-reductases for the bioreduction of sterically challenging enones.
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DOI：
10.1039/c9ra06088j
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发表时间：
2019-11-11
期刊：
影响因子：
3.9
通讯作者：
Ward, John M.
中科院分区：
文献类型：
--
作者：
Dobrijevic, Dragana;Benhamou, Laure;Aliev, Abil E.;Mendez-Sanchez, Daniel;Dawson, Natalie;Baud, Damien;Tappertzhofen, Nadine;Moody, Thomas S.;Orengo, Christine A.;Hailes, Helen C.;Ward, John M.
老黄酶家族的烯还原酶（ERs）催化活性烯烃的不对称还原，提供手性产物。它们已经成为合成化学家工具箱中的一种重要方法，为金属催化的不对称还原提供了一种可持续的替代方法。然而，开发新的生物催化烯烃还原路线需要易于获得的新型生物催化剂。一种基于序列的功能宏基因组方法被用于从排水宏基因组中鉴定新的内质网。从最初确定的10种推测的内质网酶中，8种表现出对广泛接受的单环底物的活性，其中几种内质网具有高反应产率和立体选择性。两种表现出优异的共溶剂耐受性的高性能酶被用于立体选择性还原具有立体挑战性的双环烯酮，反应以高收率进行，这是迄今为止野生型er中前所未有的。在制备酶的规模上，Hajos-Parish， Wieland-Miescher衍生物和三环酮的还原进行了良好到极好的收率。从排水宏基因组文库中提取的特殊有机耐溶剂烯还原酶是高度通用的难烯酮催化剂。
Ene-reductases (ERs) of the Old Yellow Enzyme family catalyse asymmetric reduction of activated alkenes providing chiral products. They have become an important method in the synthetic chemists' toolbox offering a sustainable alternative to metal-catalysed asymmetric reduction. Development of new biocatalytic alkene reduction routes, however needs easy access to novel biocatalysts. A sequence-based functional metagenomic approach was used to identify novel ERs from a drain metagenome. From the ten putative ER enzymes initially identified, eight exhibited activities towards widely accepted mono-cyclic substrates with several of the ERs giving high reaction yields and stereoselectivities. Two highly performing enzymes that displayed excellent co-solvent tolerance were used for the stereoselective reduction of sterically challenging bicyclic enones where the reactions proceeded in high yields, which is unprecedented to date with wild-type ERs. On a preparative enzymatic scale, reductions of Hajos–Parish, Wieland–Miescher derivatives and a tricyclic ketone proceeded with good to excellent yields. Exceptional organic solvent tolerant ene-reductases mined from a drain metagenome library are highly versatile catalysts for difficult enones.
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影响因子：
5.7
作者：
Ferrer M;Martínez-Martínez M;Bargiela R;Streit WR;Golyshina OV;Golyshin PN
通讯作者：
Golyshin PN
DOI：
10.1093/bioinformatics/btu457
发表时间：
2014-09-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Studer G;Biasini M;Schwede T
通讯作者：
Schwede T
影响因子：
5.2
作者：
Hethcox JC;Shockley SE;Stoltz BM
通讯作者：
Stoltz BM
影响因子：
5.2
作者：
Takatori, Kazuhiko;Ota, Shoya;Nagaoka, Hiroto
通讯作者：
Nagaoka, Hiroto
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE