The natural role of enzymes is to accelerate the rate of chemical reactions in living organisms; without enzymes many of these reactions would be too slow to sustain life. Enzymes have also evolved to be extremely selective, such that they perform specific reactions. The ability of enzymes to increase the rate of specific reactions also makes them useful in the chemical manufacturing industry: using enzymes to manufacture chemicals in this way is often termed ‘biocatalysis’. Biocatalysis is often thought of as a green technology, because it works at ambient temperatures and pressures, and uses water rather than potentially polluting organic solvents. Additionally, because enzymes are highly specific, biocatalysis produces few side products that would need to be removed by purification.
In our lab we discover, characterise and engineer enzymes for use as biocatalysts; such as transaminases and oxidoreductases that have potential use in the production of pharmaceuticals, fine chemicals and even plastics.
We work on the application of cofactor F420-dependent enzymes in biocatalysis. Cofactors are small molecules that some enzymes use for their chemical reactions (e.g., oxidations and reductions). Cofactor F420 is a found in a relatively small number of microbes, most of which are difficult to grow in the lab. The enzymes that use this cofactor have a lot of potential as biocatalysts for reactions including the production of chiral amines and alcohols, as well as aldehydes and ketones: reactions necessary for the production of many pharmaceuticals and fine chemicals.
Continuous-flow chemistry is a new technology for making chemicals. It is like an assembly line for building molecules, using a stream of liquid to carry the growing molecules instead of a conveyor belt. Unfortunately, enzymes are not naturally well-suited for use in continuous flow. We have developed a new engineering approach that overcomes these problems and enables biocatalysis in continuous flow reactors.
Engineered enzymes that retain and regenerate their cofactors enable continuous-flow biocatalysis. Hartley CJ, Williams CC, Scoble JA, Churches QI, North A, French NG, Nebl T, Coia G, Warden AC, Simpson G, Frazen A, Nixon Jensen C, Turner NJ & Scott C. Nature Catal. 2: 1006-1015.
Computer-guided surface engineering for enzyme improvement. Wilding M, Scott C & Warden AC. Sci. Report 8: 11998.
Cofactor F420-dependent enzymes: An under-explored resource for asymmetric redox biocatalysis. Shah MV, Antoney J, Kang SW, Warden AC, Hartley CJ, Nazem-Bokaee H, Jackson CJ, Scott C. MDPI Catal. 9 : 868.
Sugar analog synthesis by in vitro biocatalytic cascade: a comparison of alternative enzyme complements for dihydroxyacetone phosphate production as a precursor to rare chiral sugar synthesis. Hartley CJ, Scoble JM, Williams CC, Quentin QI, Frazer A, French NG, Taylor MC, Coia G, Simpson G, Turner NJ & Scott C. PLoS One 12: e0184183.