通过乳酸脱酶对基拉尔3,3,3-三二二基酸的不对称合成的研究
Jingfei Wu1, Aem Nuylert1, Misako Iwaki1
1Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan.
Chembiochem : a European journal of chemical biology
|March 27, 2025
概括
的3,3,3-三二-2-基酸 (TFLA) 生产是通过生物催化剂实现的. 乳酸脱酶和辅因子再生系统有效地从三基酸中合成光学纯的 (S) -TFLA和 (R) -TFLA.
科学领域:
- 生物催化和酶工程 生物催化和酶工程
- 有机合成 有机合成
- 制药化学 制药化学 制药化学
背景情况:
- 基拉尔3,3,3-三二-2-基酸 (TFLA) 是制药和材料的关键中间体.
- 对于其应用,TFLA异构体的酶选择性合成至关重要.
- 乳酸脱酶 (LDHs) 为TFLA生产提供了一个潜在的途径.
研究的目的:
- 开发一种生物催化方法,用于生产TFLA的两个反体.
- 选和优化乳酸脱酶,以实现高效的TFLA合成.
- 调查选定的LDHs的催化机制.
主要方法:
- 在大肠杆菌中克隆和表达来自各种生物的ldh基因.
- 使用甲酸脱酶构建尼古丁胺氨基二核酸 (NAD+) 再生系统.
- 使用重组LDH和形式脱酶,从三基酸 (TFPy) 合成TFLA的酶合成.
- 分子对接模拟以分析酶基质相互作用.
主要成果:
- 再组合的LDH和甲酸脱酶被成功表达.
- 优化的生物催化条件使得 (S) -TFLA和 (R) -TFLA的高产量和出色的立体选择性 (>99.5% ee) 成为可能.
- 特定的酶,d-LmLDH来自Leuconostoc mesenteroides和l-LDH,被确定为生产 (R) -TFLA和 (S) -TFLA的高度有效.
- 分子对接揭示了对酶的活性和对含CF3基质的立体选择性的洞察力.
结论:
- 使用乳酸脱酶和辅因子再生系统建立了一个强大的生物催化系统,用于TFLA合成.
- 使用精选的微生物和动物LDHs,可以高效地生产高度的 (S) -TFLA和 (R) -TFLA.
- 这项研究为TFLA和相关化化合物的大规模酶选择性生产提供了基础.
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