prof.dr. Ulf Hanefeld

T: +31 15 27 89304

Room C2.
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.

Chemo-enzymatic cascade reactions

Chemo-enzymatic cascade reactions are one of the mainstays of the section Biocatalysis. By combining several steps in one pot a significant step economy can be realised and the potential for environmentally benign synthesis is improved. Thus several work up steps can be avoided and pure products are ideally isolated after a series of reactions in one single vessel after just one straightforward purification step. Immobilisation of homogenous catalysts and then combining them with enzymes (Scheme 1 & 2) were developed, many of them in collaboration with other research groups. 

Scheme 1: Enantioselective reductions combined with enantioselective hydrolyses to obtain highly pure chiral intermediates (Adv. Synth. Catal. 2006, 348, 471-475 and Top. Catal. 2006, 40, 35-44.).

Scheme 2: Immobilised TEMPO as organo-catalyst in the oxidation of a sensitive alcohol to aldehyde and subsequent enantioselective cyanide addition catalysed by a Hydroxynitrile lyase (Eur. J. Org. Chem. 2006, 1672–1677).


Today the focus is shifting to redox enzymes in combination with heterogeneous catalysts, such as Pd nanoparticles (Scheme 3). For this international collaborations as well as in house production of enzymes and chemo catalysts is utilised. In this manner a wide variety of compounds is assembled enantioselectively via concise routes in high purity.


Scheme 3: 3 step sequence for the synthesis of amino alcohol via alcohol dehydrogenase and Pd nanoparticle catalysed reactions (Green Chem. DOI: 10.1039/c3gc41666f).


For other sequences and synthesis routes please contact: or

Application of enzymes in Organic Chemistry

Since the very beginning enzymes are an essential tool in organic chemistry. Although occasionally not at centre stage of chemistry their application dates back to Liebigs and Wöhlers application of Hydroxynitrile lyases 180 years ago, Emil Fischers application of enzymes in sugar chemistry, when he formulated the lock and key hypothesis and to the first enantioselective synthesis ever described (L. Rosenthaler, Biochem. Z., 1908, 14, 238-253; Scheme 1). Here again Hydroxynitrile lyases are the enzymes of choice. Indeed these enzymes are still in use in our group. Both, the immobilisation (Chem. Soc. Rev., 2013, 42, 6308 - 6321) and application in organic solvents (Chem. Eur. J. 2010, 16, 7596 – 7604), as well as new Hydroxynitrile lyases (FEBS Journal 2013, 280, 5815–5828) or their genetic modification are studied. In this way these versatile tools are modernised continuously; often in collaboration with other groups.

Scheme 1: First enantioselective reaction in chemistry. The topic is still under investigation in Delft and countless variations and additions are done.

The range of enzymes was extended since 1908 and today we study other C-C bond forming enzymes and many hydrolytic and redox enzymes.

  • Trans ketolase (Top. Catal. 2013, 56, 750–764) for the environmentally benign C-C bond synthesis starting from sugars.
  • Alcohol dehydrogenases for the enantioselective synthesis of alcohols and for ketone synthesis (see also redox enzymes)
  • Enoate reductases for the synthesis of enantiopure building blocks (see also redox enzymes)
  • Hydratases for the enantioselective addition of water to C=C bonds. Chemically this reaction is extremely difficult due to the poor nucleophilicity of water (Scheme 2)
  • Nitrile reductase, an enzyme that can reduce nitriles under mild condition (Scheme 3)

Scheme 2: Chemically the addition of water to isolated C=C and in Michael fashion is a question almost unanswered. By applying enzymes these conversions can be performed under mild conditions with high selectivity (Chem. Commun. 2011, 47, 2502–2510. and Eur. J. Org. Chem. DOI: 10.1002/ejoc.201301230).

Scheme 3: Nitrile reductase is a new class of enzymes only described recently. The scope of the E. coli enzyme is currently studied in Delft (Enz. Microb. Tech. 2013, 52, 129– 133).

For further details please contact: or


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