Nanofactories

One of the greatest challenges of the 21st century is to devise ways to make chemical manufacture less reliant on unsustainable petrochemical feedstocks and harsh chemical processes. Biocatalysis – using enzymes as catalysts – has the potential to meet this challenge.

Biocatalysis is becoming the most desirable process choice for chemical manufacture, but there are still barriers to their use in some applications, such as in continuous flow. In particular, biocatalytic processes involving energy-intensive reactions, which require an additional cofactor (helper molecule) to enable catalysis, remain unsuited to continuous flow chemistry.

Our Biocatalysis and Synthetic Biology Team have led the development of 'nanomachine' technology to address this issue. There is opportunity to for enzyme production companies and/or pharmaceutical/fine chemicals manufactures to licence the technology or to partner with us to develop this technology for particular applications and fields.

Technology

• The Nanofactories technology has relevance in biocatalysis for fine chemical/chiral chemical manufacture. Specialty enzymes are used in nearly every biotech industry from food, biorenewables, flavours and fragrances to pharmaceuticals and diagnostics.
• Certain enzymatic synthesis reactions require the addition of cofactors in order to be successful, however cofactors are expensive and are not easily recycled in flow biocatalysis systems. Our Nanofactories technology provides immobilised enzyme solutions which both retain and recycle cofactors in a flow reactor. This provides a more efficient process for the manufacture of fine chemicals and pharmaceuticals.
• The technology can be used standalone or feed in to existing manufacturing. It does not require significant infrastructure disruption and could actually reduce the footprint compared to traditional chemistry manufacturing kits.
• Currently, 14 nanomachine fusion proteins have been designed, synthesised and cloned into vectors for recombinant expression in E.coli
• Suitable candidate nanomachine fusion proteins have been expressed, purified, tethered with suitable modified cofactor and demonstrated to have comparable activity levels with both free enzymes and standard literature values for phosphorylation (ATP), oxidation (NAD+), transamination, imine reduction (NADP+) and reductive amination (NADP+) nanomachines.
• Multienzyme cascades compiling two or more nanomachine flow reactors in series have been utilised to demonstrate the continuous manufacture of the anti-diabetic iminosugar D-fagomine, and conjugated chiral amine APIs with high productivity and total turnover numbers ranging from 104 - 105.

Applications

• The preliminary application has been in the synthesis of sugar analogues (e.g. for anti-diabetic drugs) and chiral amine APIs, hence the pharmaceutical industry is the initial focus for the technology
• The Nanofactories intend to target biopharmaceutical and fine chemicals markets and estimates Serviceable addressable market (SAM) as $1 –2.5 billion in the pharmaceutical market, with a share of Market estimated at 1–10 per cent or $10–250 million
• Large public companies dominate 70 per cent of the market (Novozymes, Dupont and DSM) with key contributors being Codexis, BASF, Chr. Hansen, Amano Enzymes and AB Enzymes
• Opportunity to license to an enzyme manufacturer or pharmaceutical producer for particular fields.

Intellectual property

The team

Our team consist of biochemists, chemists and scientists with expertise around industrial processes, synthetic biology, enzymology, and structural biology including protein structure and function.