Helen Hailes: Using enzymes or sustainable starting materials to synthesise biologically active compounds

The chemical industry faces many current challenges in the preparation of compounds for use as bulk chemicals and in the pharmaceutical, agrochemical and speciality chemical industries. At present there is a high reliance on the use of fossil fuels to provide starting materials, although there is now a move towards the use of renewable resources to provide the chemical building blocks, and reagents to transform these building blocks into desired products. Waste biomass is an attractive material to use for the synthesis of chemicals, biomaterials and biofuels. In addition, in a growing bio-based economy biological catalysts (biocatalysts) such as those obtained from microorganisms and plants provide advantages over many chemical catalysts. Notably, they have been recognised as environmentally friendly, sustainable, and can be used under mild reaction conditions as well as exhibiting exquisite reaction selectivities.

At UCL we are currently investigating the use of sugar beet pulp (SBP) waste as a starting point for the sustainable synthesis of chemicals. It is currently dried and sold as animal feed, but contains many carbohydrates that could be used in synthesis. In an EPSRC funded chemical feedstocks grant we are seeking to take some of the sugars generated when the pulp is broken down (e.g. ref D. P. Ward et al), and upgrade the value by synthesising higher value compounds. An example is arabinose, a major constituent of SBP that when reacted with the enzyme transketolase, a ubiquitous enzyme in metabolic regulation, forms the product gluco-heptulose which has potential applications in hypoglycaemia (ref F. Subrizi et al).

Another major renewable chemical feedstock is furfural, which is produced from the hydrolysis and dehydration of cellulosic biomass. In recent work at UCL we have established the use of furfural starting materials in a one-pot three-step chemical cascade in water for the synthesis of polysubstitued aromatic compounds. In this work we also demonstrated the use of this methodology for the synthesis of a potential cancer chemotherapeutic (see ref Higson et al).

As a final example we are exploring the use of plant enzymes for the synthesis of bioactive alkaloids. Tetrahydroisoquinoline alkaloids are a large, diverse family of natural products that have many have pharmacological activities including the analgesic morphine. In nature, the plant enzyme norcoclaurine synthase (NCS) generates the benzylisoquinoline norcoclaurine, the first committed intermediate in the biosynthetic pathway to morphine and many other alkaloids. Recently, we have used NCS, a transaminase enzyme and the starting material dopamine in a chemoenzymatic cascades for the preparation of the alkaloids norlaudanosoline and a tetrahydroberberine. This route is efficient, low cost and sustainable, rapidly generating a complex natural product with high stereoselectivity (ref Lichman et al).