Self-sustaining closed-loop multienzyme-mediated conversion of amines into alcohols in continuous reactions
Self-sustaining closed-loop multienzyme-mediated conversion of amines into alcohols in continuous reactions
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DOI：
10.1038/s41929-018-0082-9
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发表时间：
2018-06-01
期刊：
影响因子：
37.8
通讯作者：
Paradisi, Francesca
中科院分区：
文献类型：
--
作者：
Contente, Martina L.;Paradisi, Francesca
以胺为起始原料合成醇是制备药物和聚合物的一种极好的但具有挑战性的策略。在这里，我们开发了一个多功能的，自我维持的闭环多酶平台，用于生物催化合成大范围的非市售产品，在连续流动中具有优异的收率（80至bbb99），反应时间和仲醇的光学纯度（bbb99对映体过量）。这一过程还扩展到将生物胺转化为高价值醇，如强大的抗氧化剂羟基酪醇，以及通过商业上负担得起的外消旋胺的动态动力学分解合成对映纯2-芳基丙醇。该系统利用转氨酶和氧化还原酶的原位固定化，结合成一个全自动、超高效的合成平台，具有辅助因子回收、良性副产物的在线回收和含有催化量的再生辅助因子的水介质的再循环，这将系统的效率提高了20倍以上。
The synthesis of alcohols from amine starting materials is an excellent yet challenging strategy for the preparation of pharmaceuticals and polymers. Here we developed a versatile, self-sustaining closed-loop multienzymatic platform for the biocatalytic synthesis of a large range of non-commercially available products in a continuous flow with excellent yields (80 to >99%), reaction times and optical purity of secondary alcohols (>99 enantiomeric excess). This process was also extended to the conversion of biogenic amines into high-value alcohols, such as the powerful antioxidant hydroxytyrosol, and the synthesis of enantiopure 2-arylpropanols via the dynamic kinetic resolution of commercially affordable racemic amines. The system exploits the in situ immobilization of transaminases and redox enzymes which were combined to cater for a fully automated, ultra-efficient synthetic platform with cofactor recycling, in-line recovery of benign by-products and recirculation of the aqueous media that contains the recycled cofactors in catalytic amounts, which increases the efficiency of the system by over 20-fold.