Nitrile converting biocatalysts

Nitto Chemical (now Dia-Nitrix) introduced a biosynthetic route from ACRN to acrylamide in Japan in 1985. This process uses an immobilized nitrile hydratase biocatalyst that converts the ACRN solution to acrylamide with a yield of 99.5%. This high yield allows a concentrated acrylamide solution to be made without the need for ACRN recycle or solution concentration. This process therefore has lower energy costs282. The initial plant capacity was 4,000 tonnes per year it was expanded to 20,000 tonnes per year in 1991 and that is its capacity as of 2002. 

Predominantly Rhodococcus species have been isolated as biocatalysts bearing stereoselective nitrile-converting enzymes. It has been assumed that rhodococci generally contain a nitrile hydratase/amidase system [128], but to regard this as a rule might be... 

The commercial bioconversion process employs the enzyme nitrile hydratase, which catalyzes the same reaction as the chemical process (Figure 31.15). The bioconversion process was introduced using wild-type cells of Rhodococcus or Pseudomonas, which were grown under selective conditions for optimal enzyme induction and repression of unwanted side activities. These biocatalysts are now replaced with recombinant cells expressing nitrile hydratase. The process consists of growing and immobilizing the whole cell biocatalyst and then reacting them with aqueous acrylonitrile, which is fed incrementally. When the reaction is complete the biocatalyst is recovered and the acrylamide solution is used as is. The bioconversion process runs at 10°C compared to 70°C for the copper-catalyzed process, is able to convert 100 percent of the acrylonitrile fed compared to 80 percent and achieves 50 percent concentration... 

From these results we concluded that the preferred biocatalysts for the selective hydrolysis of la, lb and Ic into the (R)-acids are, respectively, NIT-104, NIT-106 and NIT-104, although the hydrolysis of lb and Ic is rather less enantioselective than would be desirable. Thus, in a preparative experiment, NIT-104 converted la (0.1 M starting concentration) into (R)-mandelic acid (98% conversion, 98% ee), attesting that under the prevailing conditions the racemisation of the nitrile is fast... 

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. 

Lonza Fine Chemicals manufactures nicotinamide by a process in which 2-methyl-l,5-diaminopentane (a by-produa of nylon-6,6 manufacture) is first converted to 3-cyanopyridine 121 by a series of three chemically-catalyzed reactions, then the nitrile is hydrated to nicotinamide 122 (Figure 11.37) using Rhodococcus rhodochrous Jl cells immobilized in polyacrylamide particles [227-229]. A continuous feed of 3-cyanopyridine at concentrations of between 10-20 Avt /o is added in the direction of process flow, with a counter-current feed of biocatalyst in a series of stirred-tank batch bioreactors. The process generates... 

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