Enzyme Cofactor REGENERATION - Isis Project No 3387

Oxford Researchers have developed a novel system for recycling an important enzyme cofactor, nicotinamide adenine dinucleotide phosphate (NADPH).

Marketing Opportunity

Cofactors are non-protein chemical compounds that play an essential role in many enzyme catalysed biochemical reactions.  Cofactors act to transfer chemical groups between enzymes.  For example, NADPH delivers hydride ion (H-) to enzymes, thereby acting as a reducing agent.

The ability of enzymes to mediate specific and highly efficient chemical transformations under mild conditions makes them an attractive alternative to conventional organic syntheses.  Indeed, there has been growing use of enzymes as biocatalysts in the chemical and pharmaceutical industries. Redox enzymes – those that mediate oxidation or reduction reactions – form a significant subset of enzymes that are useful in industrial applications. However, most redox enzymes are dependent on expensive cofactors such as NADPH (approx. $500 for 0.75g). To date, the use of NADPH-dependent catalysts has been severely limited by the absence of industrially useful methods for recycling NADPH.

The Oxford Invention

The Oxford researchers have identified a novel family of enzymes, which enable NADPH to be recycled. The researchers have shown that the enzymes, a family of formate dehydrogenases (FDH), can be used to couple oxidation of formate to carbon dioxide with NADP+àNADPH conversion.

To demonstrate the synthetic utility of this recycling system, various NADPH-dependent oxidoreductase enzymes have been coupled with the novel FDH enzymes to obtain valuable pharmaceutical intermediates and fine chemicals (Fig. 1).  The reactions proceed with high conversions (>99%) and isolated yields (>70%), and high stereo- and enantioselectivities (typically, >99%).  The enzymes are exceptionally thermally stable and operate over a wide pH range.  Furthermore, the FDH system has the benefit of producing a gaseous bi-product (carbon dioxide) that is readily separated from the product stream.

We anticipate that this novel system will allow the use of biocatalytic routes for diverse ‘green’ chemical synthesis, on an industrial scale, that were previously unattainable due to issues of efficiency, cost and waste stream.

 

Figure 1. Biocatalytic applications of FDH-coupled NADPH regeneration.

Patent Status

This technology is the subject of an international patent application, and Isis would like to talk to companies interested in developing the commercial opportunity that this represents. Please contact the Isis Project Manager to discuss this further.

Request Further Information: Project Number 3387 - Enzyme Cofactor Regeneration