胺气处理
酮
生物转化
转氨酶
化学
生物催化
基质(水族馆)
催化作用
立体化学
组合化学
底物特异性
晶体结构
有机化学
酶
反应机理
生物
生态学
作者
Aline Telzerow,Juraj Paris,M. Håkansson,Javier González‐Sabín,Nicolás Ríos‐Lombardía,M. Schurrmann,Harald Gröger,Robert Kourist,Helmut Schwab,Kerstin Steiner
摘要
Amine transaminases are frequently used for the production of chiral amines starting from prochiral ketones. These amines can be applied as active pharmaceutical ingredients or drug precursors. However, there are still limitations to the use of amine transaminases when it comes to bulky ketone substrates, such as biaryl ketones. Using data mining, an (R)-selective amine transaminase from Exophiala xenobiotica was identified which naturally converts biaryl ketone substrates to the corresponding amines with up to 85% conversion and excellent enantioselectivity (>99% ee). Its protein crystal structure was obtained with a resolution of 1.52 A, which enabled us to explain this interesting substrate acceptance. Structure-guided protein engineering resulted in a quintuple variant with increased stability. Moreover, the amino acid exchange T273S increased the activity and broadened the substrate scope, enabling conversions of various biaryl ketones with up to >99%. A preparative biotransformation of 1-(4-(pyridin...
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