Nitrogen nitrile hydratase

Harrop, T.C. and Mascharak, P.K. (2004) Fe(III) and Co(III) centers with carboxamido nitrogen and modified sulfur coordination lessons learned from nitrile hydratase. Accounts of Chemical Research, 37, 253-260. 

The ease of the Strecker synthesis from aldehydes makes a-aminonitriles an attractive and important route to a-amino acids. Fortunately, the microbial world offers a number of enzymes for carrying out the necessary conversions, some of them highly stereoselective. Nitrilases catalyze a direct conversion of nitrile into carboxylic acid (Equation (11)), whereas nitrile hydratases catalyze formation of the amide, which can then be hydrolyzed to the carboxylic acid in a second step (Equation (12)). In a recent survey, with a view to bioremediation and synthesis, Brady et al have surveyed the ability of a wide range of bacteria and yeasts to grow on diverse nitriles and amides as sole nitrogen source. This provides a rich source of information on enzymes for future application. 

NITRILE HYDRATASE NITRILE HYDRATASE NITRITE REDUCTASE Nitrogen analogues of carbenes,... 

Many microorganisms—which should not possess nitrile reductase activity—carry out these conversions and most are relatively unspecific as to substrate. Bacteria have been screened (and taxonomically classified) for acryonitrile hydratase activity amide production and substrate and inhibition studies have been made for the nitrile hydratase from Corynebacterium spp and Rhodococcus spp and the production of acrylamide has been brought to industrial fruition Bacteria that could utilize acryonitrile as sole nitrogen and carbon source and fungi that accept aliphatic nitriles (Ci to 5) as nitrogen... 

Several synthetic Co(III) and Fe(III) complexes have been generated as models for the active-site metal center in nitrile hydratases [8, 10]. However, few have been examined in terms of water coordination and acidity. Cobalt complexes supported by Ns-type donor ligands, with two carboxamido nitrogen donors, exhibit a pfCa near 7 (Fig. 8.14a and b) [59, 60]. Introduction of two thiolate sulfur donors into the Co(III) coordination sphere increases the pK of the bound water to 8.3 (Fig. 8.14c) [61]. Interestingly, oxidation of one of the sulfur donors to a S-bound sulfmate (Fig. 8.14d) reduces the pK by around 1 unit [62]. As the active-site metal center in nitrile hydratases contain oxidatively modified cysteine residues coordinated to the metal center [8], it has been suggested that the oxidized sulfur donors play a role in modulating the acidity of the metal-bound water molecule. 

Furthermore, Agrobacterium tumefaciens d3, which was enriched on racemic 2-phen-ylpropionitrile as the sole source of nitrogen, was used for the conversion of 2-arylpro-pionitriles to the corresponding (5)-acids [63]. The conversion of both racemic 2-phenyl-propionitrile and -amide by whole cells led to the formation of the (S)-acid with an e.e. above 96% after 47.5% conversion and was caused by the combined action of an (5)-specific nitrile hydratase and a highly (5)-specific amidase (Fig, 17). The stereoselectivity of the nitrile hydratase was used for the preparation of (5)-amides by whole cells in the presence of an amidase inhibitor or with the purified nitrile hydratase [64]. The highest... 

In contrast, the nitrile hydratase of R. rhodochrous IFO 15564, which was isolated by a screening using 3-hydroxypropionitrile and benzonitrile as the sole sources of nitrogen, was found to be (5)-selective toward substituted 3-hydroxyglutaronitriles [70]. Together with an (5)-specific amidase, it converted 3-benzoyloxyglutarodinitrile to the sole product (S)-cyanocarboxylic acid in an optically pure form without leaving any intermediate ( )-cyano amide (Fig. 21). 

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