Asymmetric assembly of high-value α-functionalized organic acids using a biocatalytic chiral-group-resetting process.
Asymmetric assembly of high-value α-functionalized organic acids using a biocatalytic chiral-group-resetting process.
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DOI：
10.1038/s41467-018-06241-x
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发表时间：
2018-09-19
影响因子：
16.6
通讯作者：
Liu LM
中科院分区：
文献类型：
--
作者：
Song W;Wang JH;Wu J;Liu J;Chen XL;Liu LM
采用非手性结构单元催化组装的方法可以大大简化α-功能化有机酸的制备。然而，小氨基酸和醛的酶促组装以形成许多α-官能化有机酸是高度期望的，并且仍然是一个重大挑战。本文报道了一种人工设计的手性基团重置生物催化方法，该方法利用简单的非手性甘氨酸和醛合成立体定向的α-功能化有机酸。该级联生物催化包括基本模块和三个不同的扩展模块，并且以模块化组装方式操作。工程大肠杆菌催化剂，其中包含不同的模块（S），提供了获得α-酮酸，α-羟基酸，和α-氨基酸具有良好的转化率和对映选择性.因此，这种生物催化过程提供了一种有吸引力的策略，用于将低成本的非手性起始材料转化为高价值的α-官能化有机酸。α-官能化有机酸是许多生物活性化合物的结构单元。在这里，作者开发了一种工具箱式的模块化酶，可以重置手性基团，将非手性甘氨酸和简单的醛转化为立体定向的α-酮酸，α-羟基酸和α-氨基酸。
The preparation of α-functionalized organic acids can be greatly simplified by adopting a protocol involving the catalytic assembly of achiral building blocks. However, the enzymatic assembly of small amino acids and aldehydes to form numerous α-functionalized organic acids is highly desired and remains a significant challenge. Herein, we report an artificially designed chiral-group-resetting biocatalytic process, which uses simple achiral glycine and aldehydes to synthesize stereodefined α-functionalized organic acids. This cascade biocatalysis comprises a basic module and three different extender modules and operates in a modular assembly manner. The engineered Escherichia coli catalysts, which contained different module(s), provide access to α-keto acids, α-hydroxy acids, and α-amino acids with excellent conversion and enantioselectivities. Therefore, this biocatalytic process provides an attractive strategy for the conversion of low-cost achiral starting materials to high-value α-functionalized organic acids. Alpha-functionalized organic acids are building blocks of many bioactive compounds. Here, the authors developed a toolbox-like, modular set of enzymes that reset chiral groups, turning achiral glycine and simple aldehydes into stereodefined α-keto acids, α-hydroxy acids, and α-amino acids.
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影响因子：
4.5
作者：
Bayer, Thomas;Milker, Sofia;Rudroff, Florian
通讯作者：
Rudroff, Florian
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：
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影响因子：
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作者：
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通讯作者：
Flitsch, Sabine L.
影响因子：
4.3
作者：
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通讯作者：
Kroutil, Wolfgang
影响因子：
3.6
作者：
Adam, W;Lazarus, M;Schreier, P
通讯作者：
Schreier, P