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首页> 外文期刊>Journal of Biotechnology >Enhancing the activity and regioselectivity of lipases for 3'-benzoylation of floxuridine and its analogs by using ionic liquid-containing systems
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Enhancing the activity and regioselectivity of lipases for 3'-benzoylation of floxuridine and its analogs by using ionic liquid-containing systems

机译:通过使用含离子液体的系统,提高脂肪酶对氟尿苷及其类似物的3'-苯甲酰化的活性和区域选择性

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摘要

Ionic liquid-containing systems offered new opportunities to enzymatic acylation of nucleosides. In Pseudomonas cepacia lipase-mediated benzoylation of floxuridine (FUdR), the enzyme performances, including enzyme activity and 3'-regioselectivity, were significantly enhanced by using [C(4)MIm]PF(6)-containing systems. It was observed that the enzyme performances not only depended on the anion of IL, but also on the cation, and that a proper combination between the cation and anion was critical to allow the enzyme to exhibit excellent performances. The optimal IL content in IL-containing systems is 5% (v/v). To gain a deeper insight into enzyme recognition, we extended benzoylation of FUdR catalyzed by P. cepacia lipase to its analogs. FUdR and its analogs could be biotransformed to the desired product by P. cepacia lipase in excellent conversion (>99%) and good to excellent 3'-regioselectivity (81-99%). Furthermore, the 3'-regioselectivity of P. cepacia lipase was enhanced with the increase of hydrophobicity of 5-substituent of the substrates, due to better hydrophobic interactions with Leu287 present in the active site.
机译:含离子液体的系统为核苷的酶促酰化提供了新的机会。在假单胞菌脂肪酶介导的氟尿苷(FUdR)的苯甲酰化中,使用包含[C(4)MIm] PF(6)的系统可显着提高酶的性能,包括酶活性和3'-区域选择性。观察到酶的性能不仅取决于IL的阴离子,还取决于阳离子,并且阳离子和阴离子之间的适当组合对于使酶表现出优异的性能至关重要。含IL的系统中的最佳IL含量为5%(v / v)。为了获得对酶识别的更深入了解,我们将洋葱假单胞菌脂肪酶催化的FUdR的苯甲酰化作用扩展到了类似物。洋葱头孢霉脂肪酶可以将FUdR及其类似物生物转化为所需的产物,转化率极佳(> 99%),且3'区域选择性极好(81-99%)。此外,由于与活性位点中存在的Leu287有更好的疏水性相互作用,随着底物5位取代基疏水性的增加,洋葱头孢菌脂肪酶的3'-区域选择性也增强了。

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