Biocatalytic acid reduction scheme

Scheme 8.5 A biocatalytic (whole-cell) acid reduction scheme. AOR aldehyde oxidoreductase, ADH alcohol dehydrogenase.

Diacids. The microbial generation of mahc, fumaric, and succinic acid essentially imphes Krebs cycle pathway engineering of biocatalytic organisms to overproduce oxaloacetate as the primary four-carbon diacid that subsequently undergoes reduction and dehydration processes (Scheme 2.9). The use of these four-carbon diacids as intermediate chemicals and the state of their desirable microbial production is briefly outlined. 

Two biocatalytic routes were also developed to the pilot stage by Ciba-Geigy, namely the enantioselective reduction of the corresponding a-keto acid with immobihzed Proteus vulgaris (route A in Scheme 12.10) and with D-LDH in a membrane reactor (route B), respechvely. It was therefore of interest to compare the four approaches. The EATOS (Environmental Assessment Tool for Organic Syntheses) program was used to compare the mass consumption (kg input of raw materials for 1 kg of product) as well as other parameters [28]. 

Some OYEs have the novel biocatalytic activity of reducing aliphatic sec-nitro compounds to carbonyl compounds instead of the expected amines. This process is the biocatalytic equivalent to the Nef reaction, and it spares the use of strong acids (like H2SO4) and N2O production of the chemical alternative. The bioreduction mechanism presumably proceeds by reduction of the nitro group to the nitroso group, which subsequently tautomerizes to the more stable oxime that is further reduced to an imine derivative, which spontaneously hydrolyzes to the carbonyl compound and ammonia (Scheme 2.15). 

Formic acid (and its salts) is very commonly used as an electron donor in biocatalytic reduction reactions. Formates are cheap and the by-product CO2 evaporates easily from the reaction mixture, thereby efficiently shifting the equilibrium of the regeneration reaction. To make formate available for the regeneration of NAD(P)H, formate dehydrogenase (FDH, EC 1.2.1.2) is certainly the most widely used catalyst (Scheme 8.6) [28]. 

More recently, the focus has been put on formal nucleophilic substitution of —OH or —NH2 groups. To perform this biocatalytic variant of the Mitsunobu reaction, an oxidation-nucleophilic addition-reduction sequence is necessary, for which linked NAD-dependent oxidoreductases are ideally suited. The early contributions from the Forschungszentrum Jiilich [79] have been recently rediscovered by Kroutil and coworkers [80]. By combining a mandelate racemase (MR) with a mandelate dehydrogenase and an L-amino acid dehydrogenase, the authors could completely transform racemic mandelic acid into enantiopure (S)-phenyl-glycine (Scheme 8.16). 

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