Enoate reductase

Rohdish F, A Wiese, R Feicht, H Simon, A Bacher (2001) Enoate reductases of Clostridia. Cloning, sequencing, and expression. J Biol Chem 276 5779-5787. 

Buhler M, H Simon (1982) On the kinetics and mechanism of enoate reductase. Hoppe-Seylers Z physiol Chemie 363 609-625. 

Caldeira J, R Feicht, H White, M Teixeira, JJG Moura, H Simon, I Moura (1996) EPR and Mdssbauer spectroscopic studies on enoate reductase. J Biol Chem 271 18743-18748. 

Kuno S, A Bacher, H Simon (1985) Structure of enoate reductase from a Clostridium tyrobutyricum (C. spec. Lai). Biol Chem Hoppe-Seyler 366 463-472. 

Steinbacher, S., Stumpf, M., Weinkauf, S. et al. (2002) Enoate reductase family. In Flavins and Flavoproteins (2002), Proceedings of the 14th International Symposium, Cambridge, United Kingdom, July 14—18, pp. 941-949. 

Stuermer, R., Hauer, B., Hall, M. and Faber, K. (2007) Asymmetric bioreduction of activated C C bonds using enoate reductases from the old yellow enzyme family. Current Opinion in Chemical Biology, 11, 203-213. 

Enoate Reductase in Reduction of Triply Substituted Double Bonds... 

Enoate reductase reduces a,/3-unsaturated carboxylate ions in an NADPH-dependent reaction to saturated carboxylated anions. Useful chiral synthons can be conveniently prepared by the asymmetric reduction of a triply substituted C—C bond by the action of enoate reductase, when the double bond is activated with strongly polarizing groups [22]. Enoate reductases are not commercially available as isolated enzymes therefore, microorganisms such as baker s yeast or Clostridium sp. containing enoate reductase are used to carry out the reduction reaction. 

Another approach to preparing enantiomerically pure carboxylic acids and related compounds is via enanhoselective reduction of conjugated double bonds using NAD(P)H-dependent enoate reductases (EREDs EC 1.3.1.X), members of the so-called Old Yellow Enzyme family [44]. EREDs are ubiquitous in nature and their catalytic mechanism is well documented [45]. They contain a catalytic flavin cofactor and a stoichiometric nicotinamide cofactor which must be regenerated (Scheme 6.23). 

Simon and collaborators have described a novel stereoselective electroenzymatic reduction of alkenes of type 23 (equation 12)28. The enzyme enoate reductase is the reductant... 

Enoate reductase [153, 154], which occurs in strains of Clostridium or Proteus, and 2-oxo-acid reductase [155] from Proteus vulgaris or P. mirabilis catalyzes the stereospecific reduction of substrates performed directly by reduced methyl-viologen. No nicotinamide coenzyme is required. Methylviologen is regenerable electrochemically. Examples of the reduction of enoates, ketones, and 2-oxo acids are given in [155]. 

The generation of stereogenic centers by asymmetric reduction of carbon-carbon double-bonds is a current topic in chemoenzymatic synthesis. Though enzymes of the old yellow enzyme (OYE) family were identified to perform alkene reduction and were characterized some years ago [133-135], applications of enoate reductases in natural product syntheses are still rare. Thus, potential applications are also shown in this chapter. With an increasing number of new enoate reductases, such as YqjM reductase from B. subtilis, more and more possible targets for biotransformations can be found. 

Flail M, Stueckler C et al (2008) Asymmetric bioreduction of activated C=C bonds using Zymomonas mobilis NCR enoate reductase and old yellow enzymes OYE 1-3 from yeasts. Eur J Org Chem 2008 1511-1516... 

Values are based on the fixed Euro DKR exchange rate, 2006 data taken from the Novozymes stock report Chaparro-Riggers, J.F., Rogers, T.A., Vazquez-Figueroa, E., Polizzi, KM. and Bommarius, A.S. (2007) Comparison of three enoate reductases and their potential use for biotransformations. Adv. Synth. Catal., 349, 1521. 

Reductions catalyzed by enoate reductase enantioselective hydrogenation of a, /6-unsaturated enoates and comparable compounds. 

NADH-dependent enoate reductases are also interesting tools for synthetic applications. They stereoselectively reduce conjugated carbonyl double bonds and those activated by electron-withdrawing substituents, as shown in eqs. (4) and (5) [45],... 

The enzyme enoate reductase has been isolated and described76,11. It is a conjugated iron sulphur flavoprotein. For preparative purposes purified enoate reductase can be applied in electrochemical cells7S. In this system methyl viologen (or another artificial electron mediator for the electron transfer) is continuously regenerated by an electrode and serves as an electron donor for the reductive reaction as shown in the following diagram. 

For example78. (2 )-2-methyI-3-phenylpropanate can be prepared in the described manner in 95 % yield using the enoate reductase from Clostridium LAI. Immobilization of the enzyme 7 gives no improvement in the reaction rates in fact, when free or immobilized cells are used the reaction becomes slower. A part of the current is used for hydrogen production. 

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