通过改进的CbBVMO变种,酶合成药理相关的性硫化物
概括
工程Baeyer-Villiger单氧化酶 (BVMOs) 有效地产生性硫氧化物药物. 一种新型突变,CbBVMOv3,实现了 (R) - 兰索普拉的高产量不对称合成,具有出色的反体纯度.
科学领域:
- 生物催化剂是一种生物催化剂.
- 酶工程是什么? 酶工程是什么?
- 药用化学 医学化学
背景情况:
- 贝耶-维利格单氧酶 (BVMOs) 是催化不对称硫化物氧化过程的关键酶.
- 基拉尔硫氧化物是各种药物的合成中的重要中间体,包括像兰索普拉这样的质子抑制剂.
研究的目的:
- 设计一种高度活跃和选择性的BVMO,用于奇拉硫氧化物不对称的合成.
- 为了优化工业规模生产 (R) - 兰索普拉的酶反应条件.
主要方法:
- 构建和选兰索普拉硫化物单氧基酶CbBVMOv1.1.的组合突变库.
- 对酶合成的双相反应系统的优化.
- 在活动,选择性和基质范围方面对最佳突变体 (CbBVMOv3) 的表征.
主要成果:
- 鉴定CbBVMOv3的特定活性大约为1U mg-1的兰索普拉硫化物.
- 实现了 (R) - 兰索普拉的酶式不对称合成,具有>99%的反体过量和213g的时空产量 L-1 d-1.
- CbBVMOv3对其他硫化物表现出增强的活性,这表明其适用性更广泛.
结论:
- 工程 CbBVMOv3 是一个强大的生物催化剂,用于 (R) - 兰索普拉的高效和酶选择性合成.
- 开发的酶化工艺具有重要的潜力,可用于工业生产性硫氧化物药物.
- 这项研究强调了酶工程在制造适合制药制造的生物催化剂方面的力量.
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