CORDIS - EU research results

Biocatalytic alkylation: fitting enzymes for selective C-C bond formations

Project description

Selective and sustainable C-alkylation harnesses synthetic enzymes

Carbon is the main building block of organic compounds. Carbon-carbon bonds are fundamental linkages and among the least amenable to manipulation by synthetic chemists, their breaking and making often requiring catalysts. Alkylation of carbon (C-alkylation), the addition or substitution of an alkyl group consisting of carbon atoms bonded only to hydrogens, is one of the most important reactions. Application areas include organic chemistry, manufacturing of fuels and medicine. The EU-funded BioAlk project will build on work utilising enzymes, nature's catalysts, to facilitate the reaction. The goal is to significantly enhance selectivity to minimise undesirable products and maximise selective production of valuable and desired compounds.


Alkylation, in particular carbon-carbon (C-C) bond formation, is one of the most important and challenging synthetic transformations in chemistry. Current chemical approaches for C-alkylation require the use of expensive and toxic transition metals with complex ligands that have limited selectivity. Developing sustainable methods for the controlled formation of C-C bonds with regio- and stereospecificity in high yields has the potential to change organic chemistry and provide access to new molecules. Enzymes, Nature’s catalysts that enhance reaction rates, can selectively catalyze such reactions, with current limitations due to high energy co-substrates and the requirement for specific starting materials, sometimes leading to undesired side products, therefore unsustainable to upscale.

I aim at developing the synthetic potential of key oxidoreductase enzymes towards the sustainable selective production of highly valuable compounds through C-C bond formation. Oxidoreductases traditionally catalyze reduction and oxidation reactions and are increasingly used at industrial scale for their mild reaction conditions and exquisite chemo-, regio- and stereoselectivity. I will use the inherent mechanism of two particular oxidoreductases, ene reductases and alcohol dehydrogenases, and develop them towards selective C-C bond formation.

BioAlk aims at being disruptive in catalysis and organic synthesis by enabling new approaches for bench mark sustainable methods towards highly selective biocatalytic C-alkylation with industrially relevant oxidoreductases. I will design and develop non-natural enzymatic processes with ene reductase-catalyzed selective inter- and intramolecular α-alkylation of carbonyl and related compounds, and alcohol dehydrogenase-catalyzed nucleophilic reductive alkylation, while exploring the enzyme reaction mechanisms.

Host institution

Net EU contribution
€ 1 625 000,00
2628 CN Delft

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West-Nederland Zuid-Holland Delft en Westland
Activity type
Higher or Secondary Education Establishments
Total cost
€ 1 625 000,00

Beneficiaries (1)