prof.dr. Isabel Arends

T: +31 15 27 86659
E: I.W.C.E.Arends@remove-this.tudelft.nl

Building 58 Applied Sciences
Room B58-C1.080
Van der Maasweg 9
2629 HZ Delft
The Netherlands

 

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Enzymes as Catalysts for industrial Biotechnology

General research topic description about Enzymes as Catalysts for industrial Biotechnology will be added here soon.

Biocatalytic pathways for redox transformations

Redox enzymes (Oxidoreductases) potentially are very useful tools for organic synthesis as they allow highly selective reduction, oxidation and oxyfunctionalisation reactions (Scheme 1). [1]

Scheme 1. Selection of products obtainable via oxidoreductase catalysis.

One major challenge of oxidoreductases catalysis still is the issue of supplying the enzymes with the redox equivalents (electrons) needed for catalysis. Naturally, oxidoreductases obtain these via the reduced nicotinamide cofactor (NAD(P)H). Due to the prohibitively high price of NAD(P)H, they have to be used in catalytic amounts together with an in situ regeneration system resulting in sometimes very complicated multi enzyme cascades that are difficult to optimize and maintain robust for a long time.

One approach followed in BOC is to use cheap, synthetic analogues of the natural cofactors (Scheme 2). [2] With this concept even ‘better than naturally designed’ reaction schemes can be obtained.

Scheme 2. Enantioselective reduction of conjugated C=C-double bonds using simple NAD(P)H mimetics as stoichiometric reductants.

The most elegant source of reducing equivalents would be water. However, oxidation of water is a very difficult task due to the high thermodynamic and kinetic stability of the water molecule. Recently, we have succeeded in using visible light to promote water oxidation (catalyzed by a TiO2-catalyst) and transfer the electrons to an oxidoreductases to catalyze enantioselective reduction of conjugated C=C-double bonds (Scheme 3).[3] Thus, a highly interesting reaction concept for green and catalytic redox chemistry was established.

Scheme 3. A Photobiocatalytic reduction system. TiO2-based photocatalysts mediate the light-driven oxidation of water yielding O2 as sole by-product. The reducing equivalents liberated are transferred via flavin mediation to the active site of the oxidoreductase (here: the old yellow enzyme homologue from Thermus scotoductus SA-01).

 

Next to the above-mentioned reduction reactions also oxyfunctionalisation reactions are highly interesting for organic chemistry – especially because the current chemical catalysts are not capable of performing the introduction of oxygen into non-activated C-H-bonds with the selectivity of oxygenases. Peroxygenases represent one relatively new class of oxygenases catalyzing the selective hydroxylation of a broad range of compounds. For catalytic activity, these enzymes need H2O2, which-due to its high reactivity – has to be supplied continuously in small amounts. Recently, we have developed a photochemical system for the in situ generation of H2O2 to promote peroxygenase-catalyzed hydroxylations (Scheme 4). [4]

Scheme 4. Specific oxyfunctionalization reactions catalyzed by peroxygenases and driven by photochemical in situ generation of H2O2.

  1. a) F. Hollmann, I. W. C. E. Arends, D. Holtmann, Green Chem. 2011, 13, 2285–2313;
          b) F. Hollmann, I. W. C. E. Arends, K. Buehler, A. Schallmey, B. Buhler, Green Chem. 2011, 13, 226-265.
  2. a) C. E. Paul, I. W. C. E. Arends, F. Hollmann, ACS Catalysis 2014, 4, 788−797;
         b) C. E. Paul, S. Gargiulo, D. J. Opperman, I. Lavandera, V. Gotor-Fernández, V. Gotor, A. Taglieber, I. W. C. E. Arends, F. Hollmann, Org. Lett. 2012, 15, 180-183.
  3.      M. Mifsud, S. Gargiulo, S. Iborra, I. W. C. E. Arends, F. Hollmann, A. Corma, Nat Commun 2014
  4. a) E. Churakova, I. W. C. E. Arends, F. Hollmann, ChemCatChem 2013, 5, 565-568;
         b) E. Churakova, M. Kluge, R. Ullrich, I. Arends, M. Hofrichter, F. Hollmann, Angew. Chem. Int. Ed. 2011, 50, 10716-10719;
         c) D. I. Perez, M. Mifsud Grau, I. W. C. E. Arends, F. Hollmann, Chem. Comm. 2009, 6848 - 6850.

 

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