Oxidoreductases synthesis

All the transformations described above may be realized using various classes of enzymes. However, the importance for practical applications in organic synthesis is not the same for each class of the six enzyme classes, two are most commonly used hydrolases and oxidoreductases (altogether >85% of the total applications) [1, 3]. 

Schubert, T., Hummel, W., Kula, M.-R. and Muller, M. (2001) Enantioselective synthesis of both enantiomers of various propargylic alcohols by use of two oxidoreductases. European Journal of Organic Chemistry, (22), 4181—4187. 

The enzyme ferridoxin (Fd) NADP + oxidoreductase accepts the electron from Fd, one at a time, as it proceeds from its oxidized form through a semiquinone intermediate to its fully reduced form. The enzyme then transfers a hydride ion to NADP converting to its reduced state NADPH. Uptake of a proton in the reduction of NADP+ further contributes to the proton gradient across the thylakoid membrane driving ATP synthesis. 

Complex III (CoQ cytochrome c oxidoreductase) transfers electrons from CoQ to cytochrome c, through a sequence of cytochrome and iron-sulfur cofactors. Here, Alf for the couple CoQ/cytochrome c is 0.19 V, corresponding to a AG° of —36.7 kJ/mol, again enough to power the synthesis of an ATP molecule and to ensure that protons are pumped across the inner mitochondrial membrane. 

Oxidoreductases are, after lipases, the second most-used kinds of biocatalysts in organic synthesis. Two main processes have been reported using this type of enzymes-bioreduction of carbonyl groups [39] and biohydroxylation of non-activated substrates [40]. However, in recent few years other processes such as deracemization of amines or alcohols [41] and enzymatic Baeyer-Villiger reactions of ketones and aldehydes [42] are being used with great utility in asymmetric synthesis. 

Oxidoreductases, which catalyze oxidation-reduction reactions and are acting, for example, on aldehyde or keto groups. An important application is the synthesis of chiral molecules, especially chiral PFCs (22 out of 38 chiral products produced on large industrial scale are already made using biocatalysis). 

Fig. 5.3.7 Disorders that affect the placental/maternal synthesis of estriol and diagnostic analytes for serum and urine. ORD Oxidoreductase deficiency, STS steroid sulfatase deficiency...

Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, Chalder SM, Borucka-Ankie-wicz M, Hauffa BP, Malunowicz EM, Stewart PM, Shackleton CH (2004) Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis analytical study. Lancet 363 2128-2135... 

FIGURE 19-9 IMADH ubiquinone oxidoreductase (Complex I). Complex I catalyzes the transfer of a hydride ion from NADH to FMN, from which two electrons pass through a series of Fe-S centers to the iron-sulfur protein N-2 in the matrix arm of the complex. Electron transfer from N-2 to ubiquinone on the membrane arm forms QH2, which diffuses into the lipid bilayer. This electron transfer also drives the expulsion from the matrix of four protons per pair of electrons. The detailed mechanism that couples electron and proton transfer in Complex I is not yet known, but probably involves a Q cycle similar to that in Complex III in which QH2 participates twice per electron pair (see Fig. 19-12). Proton flux produces an electrochemical potential across the inner mitochondrial membrane (N side negative, P side positive), which conserves some of the energy released by the electron-transfer reactions. This electrochemical potential drives ATP synthesis. 

The reaction [Eq. (7)] requires a disulfide-reducing system such as dithiothreitol or disulfide reductase and a reducing agent such as NADPH or reduced ferredoxin. It is proposed [Eq. (5)] that carbon monoxide oxidoreductase binds CO as a one-carbon intermediate [C,], which can be either oxidized to C02 or condensed with the methyl group of a methylated corrinoid protein and CoA in the final step of acetyl-CoA synthesis. 

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