Biocatalysis nitrile hydratase

DiCosimo, R. (2007) Nitrilases and nitrile hydratases, in Biocatalysis in the Pharmaceutical and Biotechnology Industries (ed. R.N. Patel), CRC Press LLC, Boca Raton, FL, Chapter 1. 

In summary, the formation of optically active compounds through hydrolysis reactions is dominated by biocatalysis mainly due to the availability and ease of use of a wide variety of esterases, lipases and (to a lesser extent) acylases. Epoxide ring-opening (and related reactions) is likely to be dominated by salen-metal catalysts while enzyme-catalysed nitrile hydrolysis seems destined to remain under-exploited until nitrilases or nitrile hydratases become commercially available. 

Although biocatalysis is the new kid on the block, more and more companies are using enzymes for chemical manufacture. One reason for this is that biocatalysts give sustainable alternatives to chemical manufacture, and not just for making chiral products. The synthesis of acrylamide via an enzyme-catalyzed water addition to acrylonitrile (2-propenenitrile) is a classic example (Figure 1.15). It uses the Rhodo-coccus enzyme nitrile hydratase. Commercialized in 1985 by Nitto Chemicals in... 

Utilising an overexpressed nitrile hydratase from Rhodococcus rhodochrous in immobilised cells 30000 tons per year are produced by Mitsubishi Rayon Co. Ltd. The selectivity of the nitrile hydratase is 99.99% for the amide, virtually no acrylic acid is detected and since all starting material is converted yields are excellent (>99%). The time space yield is 2 kg product per liter per day (Scheme 6.37). This clearly demonstrates the power of biocatalysis. 

Fischer-Colbrie, G., Herrmaim, M., Henmann, S., Pnolakka, A., Wirth, A., Cavaco-Panlo, A., and Gnebitz, G.M. 2006. Surface modification of polyacrylonitrile with nitrile hydratase and amidase from Agrobacterium tumefaciens. Biocatalysis and Biotransformation, 24 419-25. 

Biotransformations for the synthesis of asymmetric compounds can be divided into two types of reactions those where an achiral precursor is converted into a chiral product (true asymmetric synthesis) and those involving the resolution of a racemic mixture. Both types of reaction are used at Lonza, which is a leading producer of intermediates for the life science industry. Lonza also uses biocatalysis for the synthesis of achiral molecules, for example, an immobilized whole-cell biocatalyst is used for the nitrile hydratase-catalyzed synthesis of thousands of tons per year of nicotinamide from 3-cyanopyridine. 

An enzymatic acrylonitrile hydration was first patented in 1981 8nitrile hydratases of different origin have been shown to be able to convert acrylonitrile into acrylamide. However, a major problem associated with biocatalysis for production of acrylonitrile is the short half-life of the enzyme due to substrate and product inhibition. Acrylonitrile is a strong alkylating agent which reacts by Michael addition with the sulfhydryl groups of proteins f 8, 69L... 

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