Crotonase Catalysis Enables Flexible Production of Functionalized Prolines and Carbapenams
Crotonase Catalysis Enables Flexible Production of Functionalized Prolines and Carbapenams
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DOI：
10.1021/ja208318d
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发表时间：
2012-01-11
影响因子：
15
通讯作者：
Schofield, Christopher J.
中科院分区：
文献类型：
--
作者：
Hamed, Refaat B.;Henry, Luc;Schofield, Christopher J.
The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereo-selective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding beta-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic beta-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers.
