Biocatalytic access to betazole using a one-pot multienzymatic system in continuous flow.
Biocatalytic access to betazole using a one-pot multienzymatic system in continuous flow.
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DOI：
10.1039/d1gc01095f
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发表时间：
2021-05-24
期刊：
影响因子：
--
通讯作者：
Paradisi F
中科院分区：
文献类型：
--
作者：
Romero-Fernandez M;Paradisi F
为替代传统的合成方法生产倍唑类药物，开发了一种以醇为前体的单锅生物催化体系。ω-转氨酶，乙醇脱氢酶和用于原位辅因子回收的水形成NADH氧化酶被联合催化该反应，在与可溶性酶的间歇反应中产生75%的摩尔转化率。然后，通过新建立的基于甲基丙烯酸酯的多孔载体的顺序功能化协议，该多酶系统被共同固定，从而为每种酶定制固定化学物质。该多催化系统在连续流填充床反应器中建立，在15分钟的停留时间内产生高达2.59 g L−1 h−1的时空产率，并通过分段气液流持续供应氧气用于原位辅因子回收。增加了一个在线捕获和释放柱，使产品回收率达到80%。在一锅连续流生物催化级联反应中，利用PBR承载多酶共固定系统，在恒定的氧气供应下进行原位辅因子循环，合成了倍唑的伯胺，产率为2.59 g L−1 h−1。
As an alternative to classical synthetic approaches for the production of betazole drug, a one-pot biocatalytic system for this pharmaceutical molecule from its alcohol precursor has been developed. An ω-transaminase, an alcohol dehydrogenase and a water-forming NADH oxidase for in situ cofactor recycling have been combined to catalyse this reaction, yielding 75% molar conversion in batch reactions with soluble enzymes. This multienzyme system was then co-immobilised through a newly established protocol for sequential functionalization of a methacrylate-based porous carrier to enable tailored immobilisation chemistries for each enzyme. This pluri-catalytic system has been set up in a continuous flow packed-bed reactor, generating a space–time yield of up to 2.59 g L−1 h−1 with 15 min residence and a constant supply of oxygen for in situ cofactor recycling through a segmented air–liquid flow. The addition of an in-line catch-and-release column afforded >80% product recovery. The primary amine of betazole is synthesised from an alcohol in a one-pot, continuous flow biocatalytic cascade, using a PBR hosting a multienzyme co-immobilised system with constant O2 supply for in situ cofactor recycling, yielding 2.59 g L−1 h−1.
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影响因子：
6.2
作者：
Mateo, C;Torres, R;Fernández-Lafuente, R
通讯作者：
Fernández-Lafuente, R
DOI：
10.1126/science.aac9283
发表时间：
2015-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mutti FG;Knaus T;Scrutton NS;Breuer M;Turner NJ
通讯作者：
Turner NJ
影响因子：
2.6
作者：
Fernandez-Lorente, Gloria;Lopez-Gallego, Fernando;Guisan, Jose M.
通讯作者：
Guisan, Jose M.
影响因子：
3.2
作者：
Nowak, Claudia;Pick, Andre;Sieber, Volker
通讯作者：
Sieber, Volker
影响因子：
2.6
作者：
da Rocha, J. R. M.;Ribeiro, U.;Szachnowicz, S.
通讯作者：
Szachnowicz, S.