Efficient chemoenzymatic synthesis of gabapentin by control of immobilized biocatalyst activity in a stirred bioreactor
2017
Xue, Ya-Ping | Zhong, Hu-Jun | Zou, Shu-Ping | Zheng, Yu-Guo
Gabapentin has been widely used for the treatment of epilepsy and neuropathic pain in the world. In this work, an efficient and greener chemoenzymatic manufacturing process for gabapentin has been developed. The whole cells expressing engineered nitrilase were immobilized in diatomite cross-linked with polyethyleneimine and glutaraldehyde to improve their reusability and stability for the synthesis of gabapentin intermediate 1-cyanocyclohexaneacetic acid from 1-cyanocyclohexaneacetonitrile. The initial enzyme activity in the bioreactors at each batch biotransformation was maintained at a constant value by introducing fresh immobilized cells into the system to keep the high conversion (100%) and the same operation time (8h) in each batch. The resulting 1-cyanocyclohexaneacetic acid was then converted to gabapentin efficiently by simple chemical steps. An E factor (exclude water) of 11.5 was calculated for the chemoenzymatic route relative to 55.7 for the mentioned chemical process. This new route dramatically improved process efficiency compared to the chemical process.
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