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Functional characterization of salt-tolerant microbial esterase WDEst17 and its use in the generation of optically pure ethyl (R)-3-hydroxybutyrate.

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机构: [1]CAS Key Laboratory of Tropical Marine Bio‐Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong, China [2]Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong, China [3]Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China [4]South China Sea Bio‐Resource Exploitation and Utilization Collaborative Innovation Center, Guangzhou, Guangdong, China
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关键词: ethyl (R)‐3‐hydroxybutyrate kinetic resolution novel esterase opposite enantio‐selectivity process optimization

摘要:
The two enantiomers of ethyl 3-hydroxybutyrate are important intermediates for the synthesis of a great variety of valuable chiral drugs. The preparation of chiral drug intermediates through kinetic resolution reactions catalyzed by esterases/lipases has been demonstrated to be an efficient and environmentally friendly method. We previously functionally characterized microbial esterase PHE21 and used PHE21 as a biocatalyst to generate optically pure ethyl (S)-3-hydroxybutyrate. Herein, we also functionally characterized one novel salt-tolerant microbial esterase WDEst17 from the genome of Dactylosporangium aurantiacum subsp. Hamdenensis NRRL 18085. Esterase WDEst17 was further developed as an efficient biocatalyst to generate (R)-3-hydroxybutyrate, an important chiral drug intermediate, with the enantiomeric excess being 99% and the conversion rate being 65.05%, respectively, after process optimization. Notably, the enantio-selectivity of esterase WDEst17 was opposite than that of esterase PHE21. The identification of esterases WDEst17 and PHE21 through genome mining of microorganisms provides useful biocatalysts for the preparation of valuable chiral drug intermediates. © 2018 Wiley Periodicals, Inc.

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出版当年[2017]版:
大类 | 4 区 医学
小类 | 4 区 分析化学 4 区 药物化学 4 区 有机化学 4 区 药学
最新[2025]版:
大类 | 3 区 化学
小类 | 3 区 有机化学 4 区 分析化学 4 区 药物化学 4 区 药学
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第一作者机构: [1]CAS Key Laboratory of Tropical Marine Bio‐Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong, China [2]Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong, China
通讯作者:
通讯机构: [1]CAS Key Laboratory of Tropical Marine Bio‐Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong, China [2]Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong, China [4]South China Sea Bio‐Resource Exploitation and Utilization Collaborative Innovation Center, Guangzhou, Guangdong, China [*1]CAS Key Laboratory of Tropical Marine Bio‐Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong 510301, China.
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