Jennifer A Littlechild
University of Exeter, UK
Title: Thermophilic enzymes with applications for industrial biocatalysis
Biography
Biography: Jennifer A Littlechild
Abstract
There is an increasing demand for new enzymes with enhanced performance and/or novel functionalities that provide savings in time, money and energy for industrial processes in the areas of high value chemical production and other white biotechnology applications. Only a small proportion of nature’s catalysts have been utilised for industrial biotechnology. The number of enzymes explored to date remains within the range of 1-2% of known biodiversity. A problem with using enzymes for industrial biocatalysis reactions is often their stability under the harsh conditions employed. The use of naturally thermostable enzymes isolated from hot environments are more stable to high temperatures, extremes of pH and exposure to organic solvents. The projects HOTZYME and THERMOGENE have identified hydrolase and transferase enzymes of industrial interest isolated from high temperature environments around the world. These have been isolated from thermophilic bacterial and archaeal genomes and metagenomes. A selection of these novel thermostable enzymes including cellulases, carboxylesterases, lactonases, epoxide hydrolases, transketolases, hydroxymethyl transferases and transaminases have been characterized both biochemically and structurally. Transaminase enzymes have received special attention for the production of chiral amines which are important building blocks for the pharmaceutical industries. These enzymes catalyse the reversible transfer of an amino group from a donor substrate onto a ketone/aldehyde or sugar acceptor molecule. They can be subdivided into 6 classes. The less studied class 4 (branched chain) (R) selective, class 5 (S) selective and class 6 (sugar) enzymes have been identified. An example of the archaeal class 4 enzyme from Archaeoglobus fulgidus; a thermostable class 5 archaeal transaminase from Sulfolobus solfataricus and class 6 sugar transaminase from A. fulgidus. Two new enzymes with interesting substrate specificity and stereo-selectivity have been discovered which have already been demonstrated at industrial scale for the production of new chiral chemical building blocks.
References:
- Littlechild J A (2017) Improving the ‘tool box’ for robust industrial enzymes. J. Industrial Microbiology and Biotechnology, 44(4-5):711–720.
- William Finnigan, Adam Thomas, Holly Cromar, Ben Gough, Radka Snajdrova, Joe Adams, Jennifer A Littlechild and Nicholas J Harmer (2017) Characterization of carboxylic acid reductases as enzymes in the toolbox for synthetic chemistry. ChemCatChem, 9:1005-1017.
- Sayer C, Finnigan W, Isupov M, Levisson M, Kengen S, van der Oost J, Harmer N and Littlechild J A (2016) Structural and biochemical characterisation of Archaeoglobus fulgidus esterase reveals a bound CoA molecule in the vicinity of the active site. Scientific Reports, 6:25542.
- Zarafeta D, Kissas D, Sayer C, Gudbergsdottir S R, Ladoukakis E, Isupov M N, Chatziioannou A, Peng X, Littlechild J A, Skretas G and Kolisis F N (2016) Discovery and characterisation of a thermostable and highly halotolerant GH5 cellulose from an Icelandic hot spring isolate. PLoS ONE 11(1):07.