Science: new bio-inspired chemistry for amine synthesis

Cleaner, more efficient and more sustainable.

24 September 2015

A new biocatalytic conversion route developed by researchers from the University of Amsterdam (UvA) and published this week in Science holds the promise for a cleaner and more efficient industrial synthesis of amines – which are important chemical starting materials for the manufacture of products like medicines and plastics. This new 'artificial enzymatic pathway' outperforms all other (non-biocatalytical) conversion methods in terms of versatility, efficiency and the reduction of waste. Furthermore, it can facilitate the use of biomass as a sustainable resource for amines, replacing oil.

The new sustainable conversion route, based on the concurrent use of two modified enzymes, was developed by Francesco Mutti and his coworkers at the Biocatalysis laboratories of the Van 't Hoff Institute for Molecular Sciences (HIMS) in collaboration with the University of Manchester and BASF. A patent application has been filed. The work forms part of the UvA’s Sustainable Chemistry research priority area.

New bio-inspired chemistry for amine synthesis

The new biocatalytic system converts (biobased) alcohols to amines and consists of the enzymes alcohol dehydrogenase (ADH) and amine dehydrogenase (AmDH).

Enzymes as catalyst

Making chemical processes more efficient in terms of energy and waste often depends on the improvement or replacement of the used catalyst. Traditionally, these auxiliary substances consist of rather simple and robust molecules or compounds. Although these enable the desired chemical conversion they don’t necessarily do so in the most sustainable way. To accomplish this, more elaborate and sophisticated compounds are being developed that reduce the need for energy, minimise the production of waste and – increasingly – enable the use of biobased feedstock.

Dr Mutti and his Biocatalysis group are successfully pursuing a new and promising approach in which modified enzymes are used as catalysts. Enzymes are large elaborate protein molecules that enable the chemical conversions in living cells, some of which have become highly efficient as a result of evolutionary changes.

Cleaner and more efficient

In the field of biocatalysis appropriate natural enzymes are identified in microorganisms such as bacteria and yeasts and are subsequently optimised for a desired chemical conversion by means of so-called enzyme engineering.

Because enzymes are intrinsically compatible with each other, they can easily be combined in a one-pot process carrying out sequential reactions without the need for intermediate isolation and purification steps. Hence the overall biocatalytic process is more efficient and produces less waste than traditional chemical processes.

Versatile amine synthesis

In the current issue of   Science, the researchers at HIMS successfully demonstrate the catalytic enzymatic conversion of alcohols to amines. A particularly relevant aspect is that the developed process proceeds in a redox self-sufficient manner, internally recycling electrons.

Francesco Mutti

Dr Francesco Mutti, group leader Biocatalysis, has recently obtained an ERC Starting Grant. Photograph by Attilio Barcella.

Amines (chemical compounds containing an amino group, -NH 2) are among the most frequently used chemical intermediates for the production of pharmaceuticals, fine chemicals, agrochemicals, polymers, dyestuffs, pigments, emulsifiers and plasticizing agents. In recent decades many academic and industrial researchers have worked on efficient methods for synthesizing these amines starting from alcohols (chemical compounds containing a hydroxyl group, -OH). The new enzymatic method now reported in  Science outperforms all other (non-biocatalytical) conversion methods in terms of versatility, efficiency, selectivity and reduction of waste.

This novel method relies on two enzyme classes, alcohol dehydrogenases and  amine dehydrogenases that work in tandem in a so-called hydrogen-borrowing cascade, a process wherein electrons are internally recycled, making it redox self-sufficient. It possesses the highest possible atom efficiency, sourcing nitrogen from ammonia and generating water as the sole by-product. One particularly important feature is that it gives direct access to highly valuable enantiopure amines, which constitute the active core of a large number of pharmaceuticals and fine chemicals.

Renewable resources

Another important aspect is that the new 'artificial enzymatic pathway' facilitates the use of biomass as a sustainable resource for amines, replacing oil. Renewable resources like carbohydrates or lignin abundantly contain molecules with hydroxyl functionalities. They are also the main functional group of alcohols that are obtained, for instance, by fermentation of biomass.

Going forward Mutti and his group plan to integrate the biocatalytic hydrogen-borrowing amination into more general ‘extended artificial pathways’  for the conversion of cheap starting material (ideally originated from biomass) into valuable chemicals. For this further enzymatic engineering will be necessary, in particular of the amine dehydrogenases.


Francesco G. Mutti, Tanja Knaus, Nigel S. Scrutton, Michael Breuer, Nicholas J. Turner: Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades. Science, 25 September 2015: Vol. 349 no. 6255 pp. 1525-1529.

Published by  HIMS