Highly regioselective and efficient production of 1‐cyanocyclohexaneacetamide by Rhodococcus aetherivorans ZJB1208 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 (g product /g cat ) 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