Advancing green chemistry through enzyme biocatalysis

Producing chemicals can be harmful to the environment, especially when conducted on an industrial scale. In the pursuit of greener technology, Professor Gary Black and colleagues from the Exploring and Exploiting Microbial Diversity research group have conducted over a decade of research on the process of biocatalysis (the use of enzymes in chemical synthesis), exploring the extent to which this technique is a viable alternative to more traditional methods. Expertise generated through this research has proved commercially beneficial for Prozomix, a UK-based company specialising in the discovery and production of biocatalysis enzymes, helping generate new products and production pathways that have boosted their income and reputation as a world-leader in the field, with a customer base including 10 of the 11 leading pharmaceutical companies. 

Many useful and important ingredients for producing pharmaceuticals are made in high temperature, extreme acidic or alkaline environments, and require reactions that create significant quantities of unwanted by-products. These chemical synthesis routes are therefore energy and resource intensive and create a lot of waste. The process of biocatalysis – the use of natural catalysts, such as enzymes, to accelerate chemical reactions – as a ‘green’ alternative has grown substantially in popularity in line with increasing concerns about the environmental impact and sustainability of industrial activities.  

Professor Black and colleagues have developed a quick and simple method for identifying suitable biocatalytic enzymes for converting nitriles – chemicals that are part of many pharmaceuticals – but challenging to convert using traditional chemical synthesis techniques. This new method involves screening many different enzymes in ‘panels’ comprised of small wells containing ingredients for the nitrile conversion. If the enzyme is active, the colour indicator turns a shade of blue, identifying suitable enzymes to catalyse the desired reaction. These panels have since been marketed and sold by Prozomix as ‘enzyme toolkits’, which has enabled them to become a global player in the enzyme screening market. 

Prozomix have benefitted further from work led by Professor Darren Smith into metagenomics, the use of DNA-sequencing to identify microbial genes within environmental samples. Metagenomics allows the pool of enzymes available for chemical reactions to be greatly expanded as it enables screening of novel and diverse enzymes present in the environment. This process led to the identification of the new ketoreductase (KRED) enzymes known to be useful in the production of pharmaceutical ingredients. Following this discovery Professor Black and colleagues developed another novel colour indicator specific to this enzyme family, which has since been branded and sold by Prozomix as a product known as ‘kREDy-to-go™’. This approach has made the screening of enzymes much cheaper, easier and quicker for Prozomix’s customers. 

Northumbria’s collaboration with Prozomix also led to the development of another highly desirable panel of enzymes known as cytochrome P450s, whose properties have enabled Prozomix to enter the drug metabolism market, generating significant new income for the company. 

The ongoing partnership between Professor Black and Smith’s teams and Prozomix has been integral to the growth of the business over the past decade, resulting in significant investment in new manufacturing space, equipment and staff. Indeed, current expansion of Prozomix’s fermentation capacity will mean it will soon become the only company in the sector able to offer initial enzyme discovery through to production at the same site.