New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates
文献类型：期刊论文
| 作者 | Li, Guangyue1,2; Yao, Peiyuan1,2; Cong, Peiqian1,2; Ren, Jie1,2; Wang, Lei1,2; Feng, Jinhui1,2; Lau, Peter C. K.1,2,3,4; Wu, Qiaqing1,2; Zhu, Dunming1,2 |
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2016-05-03 |
| 卷号 | 6 |
| 英文摘要 | To further expand the substrate range of the cyclohexylamine oxidase (CHAO) from Brevibacterium oxydans, a library of diverse mutants was created and assayed toward a group of structurally diverse substrates. Among them, mutants T198A and M226A exhibited enhanced activity relative to wt CHAO for most (S)-enantiomers of primary amines and some secondary amines. While mutants T198I, L199I, L199F, M226I and M226T were more active than wt CHAO toward the primary amines, mutants T198F, L199T, Y321A, Y321T, Y321I and Y321F enhanced the enzyme activity toward the secondary amines. In particular, mutant Y321I displayed an enhanced catalytic efficiency toward 1-(4-methoxybenzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydroisoquinoline (13). Whereas a double mutant, Y321I/M226T, acted on (S)-N-(prop-2-yn-1-yl)-2, 3-dihydro-1H-inden-1-amine [(S)-8]. Since (R)-8 is an irreversible inhibitor of monoamine oxidase and (S)-13 is an intermediate of dextromethorphan, a cough suppressant drug, deracemizations of 8 and 13 were carried out with crude enzyme extracts of the respective mutants. This resulted in 51% and 78% isolated yields of (R)-8 and (S)-13, respectively, each with high enantiomeric excess (93% and 99% ee). The results demonstrated the application potential of the evolved CHAO mutants in drug synthesis requiring chiral secondary amines. |
| WOS标题词 | Science & Technology |
| 类目[WOS] | Multidisciplinary Sciences |
| 研究领域[WOS] | Science & Technology - Other Topics |
| 关键词[WOS] | ASYMMETRIC-SYNTHESIS ; DIRECTED EVOLUTION ; KINETIC RESOLUTION ; CHIRAL AMINES ; DERACEMISATION ; RASAGILINE ; ENANTIOSELECTIVITY ; HYDROGENATION ; ACID |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000375291300001 |
| 源URL | [http://124.16.173.210/handle/834782/2261]  |
| 专题 | 天津工业生物技术研究所_生物催化与绿色化工 朱敦明_期刊论文 |
| 作者单位 | 1.Chinese Acad Sci, Natl Engn Lab Ind Enzymes, Tianjin Airport Econ Area, 32 Xi Qi Dao, Tianjin 300308, Peoples R China 2.Chinese Acad Sci, Tianjin Engn Ctr Biocatalyt Technol, Tianjin Inst Ind Biotechnol, Tianjin Airport Econ Area, 32 Xi Qi Dao, Tianjin 300308, Peoples R China 3.McGill Univ, Dept Chem, Montreal, PQ H3A 2B4, Canada 4.McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada |
| 推荐引用方式 GB/T 7714 | Li, Guangyue,Yao, Peiyuan,Cong, Peiqian,et al. New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates[J]. SCIENTIFIC REPORTS,2016,6. |
| APA | Li, Guangyue.,Yao, Peiyuan.,Cong, Peiqian.,Ren, Jie.,Wang, Lei.,...&Zhu, Dunming.(2016).New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates.SCIENTIFIC REPORTS,6. |
| MLA | Li, Guangyue,et al."New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates".SCIENTIFIC REPORTS 6(2016). |
入库方式： OAI收割
来源：天津工业生物技术研究所
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