疏水性氨基酸的羟基化研究进展

Advances in hydroxylation of hydrophobic amino acid

摘要:

羟基化氨基酸在生物技术和分子生物学中具有独特价值，具有抗真菌、抗菌、抗病毒和抗癌的特性。通过比较化学合成与生物催化合成羟基氨基酸的异同，选择具有高对映结构选择性的生物催化合成方法成为羟基氨基酸合成的首选。生物催化实现疏水性氨基酸的羟基化和羟化酶紧密相关，而羟化酶又是单核非血红素Fe(Ⅱ) 和α-酮戊二酸依赖型双加氧酶 (Fe/αKGDs) 的一种，Fe/αKGDs存在共性催化机制。因此，疏水性氨基酸在被催化的过程中，会利用关键中间体高价铁-超氧复合体 (Fe(Ⅳ)=O) 引起多种氧化转化，从而完成羟基化过程。文中就疏水性氨基酸的羟基化合成及功能应用，尤其是 (2S,3R,4S)-4-羟基-异亮氨酸 (4-HIL) 和羟脯氨酸，进行了详细的阐述，探讨了Fe/αKGDs的共性催化反应机制，并对羟基氨基酸在基础研究和工业中的应用进行了综述。

Abstract:

Hydroxy amino acids, constituents of chiral pharmaceutical intermediates or precursors, have a variety of unique functions in the research fields of biotechnology and molecular biology, i.e. antifungal, antibacterial, antiviral and anticancer properties. Biosynthesis of hydroxy amino acids is preferred because of its high specificity and selectivity. The hydroxylation of hydrophobic amino acids is catalyzed by hydroxylase, which belongs to the mononuclear non-heme Fe(Ⅱ)/α-ketoglutarate-dependent dioxygenases (Fe/αKGDs). Fe/αKGDs utilize an (Fe(Ⅳ)=O) intermediate to activate diverse oxidative transformations with key biological roles in the process of catalytic reaction. Here, we review the physiological properties and synthesis of hydroxy amino acids, especially for the 4-HIL and hydroxyproline. The catalytic mechanism of Fe/αKGDs is elucidated, and the applications of hydroxy amino acids in industrial engineering are also discussed.