Highly regioselective and efficient production of 1-cyanocyclohexaneacetamide byRhodococcus aetherivoransZJB1208 nitrile hydratase

BACKGROUND The regioselective hydration of alicyclic α,ω-dinitrile 1-cyanocyclohexaneacetonitrile (1-CCHAN), followed by hydrogenation of ω-cyano group is a green and elegant route to gabapentin. As the selective chemical hydration of dinitrile is virtually impossible, a bioprocess for regioselective hydration of 1-CCHAN was developed using microbial nitrile hydratase. RESULTS A newly isolated NHase producing strain, Rhodococcus aetherivorans ZJB1208, was successfully used for hydration of 1-CCHAN. Some key parameters of the biocatalytic process, including reaction temperature, pH, catalyst loading and substrate loading, were optimized. The fed-batch biotransformation was performed in non-buffered water system with the continuous precipitation of 1-cyanocyclohexaneacetamide. The substrate loading was increased up to 864 g L−1 (6.0 mol L−1), giving a product concentration of 966.7 g L−1 and biocatalyst yield (gproduct/gcat) of 204.2. CONCLUSION This study is the first example of microbial nitrile hydratase with both excellent regioselectivity and strong substrate tolerance for alicyclic dinitrile and affords a potentially industrial route to gabapentin. © 2015 Society of Chemical Industry