Asymmetric reductive amination by a wild-type amine dehydrogenase from the thermophilic bacteria Petrotoga mobilis
Asymmetric reductive amination by a wild-type amine dehydrogenase from the thermophilic bacteria Petrotoga mobilis
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DOI：
10.1039/c6cy01625a
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发表时间：
2016-01-01
影响因子：
5
通讯作者：
Vergne-Vaxelaire, Carine
中科院分区：
文献类型：
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作者：
Mayol, Ombeline;David, Sylvain;Vergne-Vaxelaire, Carine
生物催化酮还原胺化合成手性胺是最具挑战性的反应之一。使用基因组挖掘方法，我们发现催化酮的还原胺化的蛋白质在α或β位置没有羧基官能团。利用运动石油袍菌产的热活性胺脱氢酶（AmDH）AmDH 4合成了（4S）-4-氨基戊酸（ee ≥ 99.5%），产率88%。高稳定性和底物耐受性使AmDH 4成为进一步发现具有扩大底物范围的还原胺化生物催化剂的非常好的起点。这是野生型酶与具有适当NAD（P）H-AmDH活性的相关基因的首次报道。
The biocatalytic reductive amination of ketone to chiral amine is one of the most challenging reactions. Using a genome-mining approach, we found proteins catalyzing the reductive amination of ketones without a carboxylic function in the alpha or beta position. The synthesis of (4S)-4-aminopentanoic acid (ee >= 99.5%) was achieved with the thermoactive amine dehydrogenase (AmDH) AmDH4 from Petrotoga mobilis in 88% yield. The high stability and substrate tolerance make AmDH4 a very good starting point for further discovery of reductive amination biocatalysts with an enlarged substrate range. This is the first report of wild-type enzymes with related genes having proper NAD(P)H-AmDH activity.