Development of alcohol dehydrogenase (ADH) and ene-reductase (ERED) enzymes for the production of enantiopure sulphur-containing flavours and fragrances.

Dr Daniele Castagnolo, School of Cancer and Pharmaceutical Sciences, King's College London.
Dr Sarah Barry, Department of Chemistry, King's College London.
Dr Beatriz Dominguez , Johnson Matthey

project details

Volatile sulphur compounds constitute a wide class of chemicals containing at least a C-S bond and contributing to both agreeable and disagreeable flavours and fragrances of foods and beverages. Most volatile sulphur compounds exist as chiral isomers and the olfactory perception of them depends often on the confirguration of the C-S stereocentre. For example, the (R)-enantiomer of 3-thio-hexanol has a tropical fruit aroma, while the (S)-enantiomer has a grassy smell. From the perspective of flavours and fragrances industrial manufacturing, the synthesis of VSC represents a challenge due to their natural volatility, low chemical stability and different reactivity of sulphur compounds incompatible with the standard asymmetric chemistry methods. Even if challenging, the economic reward is high, making chemical and F&F industries keen to identify new strategic research to develop mild, economically-viable, more efficient, selective and sustainable manufacturing routes.

In collaboration with Johnson Matthey, that has world leading experience in the manufacturing of chemicals, including flavours and fragrances, a new industrially sustainable approach for the synthesis of volatile sulphur compounds will be developed within this project. Two classes of biocatalysts will be investigated, namely the alcohol dehydrogenases (ADH) and the ene-reductases (ERED). These enzymes will be used to synthesise volatile sulphur compounds coating a C-S bond in a stereoselective manner. The best enzymes will be further optimised (i.e. via directed evolution) to expand the scope of these new methodologies

The project includes a placement in Johnson Matthey (3-6 months) where the candidate will be trained in molecular biology, enzymology and biocatalsyis. This project is highly interdisciplinary, combining chemical synthesis and analytical chemistry with enzyme evolution, molecular biology and F&F manufacturing processes.

eligibility and application

Applicants must hold, or be expected to achieve, a first or high upper second-class undergraduate honours degree or equivalent (for example BA, BSc, MSci) or a Masters degree in a relevant subject. This project is funded by a 4-year BBSRC studentship, applicants should ensure they have understood the funding eligibility criteria for these studentships. Unfortunately international students are not eligible for programme funding on this project.

The ideal candidate for this project would hold a Master’s degree in chemistry or chemistry related subjects (i.e. pharmaceutical chemistry, analytical chemistry etc). The candidate must have an excellent knowledge of organic chemistry as background. Expertises and interest in enzymatic chemistry, biochemistry, biocatalysis, process chemistry and molecular biology are recommended but not mandatory.

For more information regarding the project, please contact Dr Daniele Castagnolo

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