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

  • Full or part time
  • Application Deadline
    Friday, January 24, 2020
  • Funded PhD Project (UK Students Only)
    Funded PhD Project (UK Students Only)

Project Description

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.


Applications must be complete, including both references, by 24th January 2020

Funding Notes

Fully funded place including home (UK) tuition fees and a tax-free stipend in the region of £17,009. Students from the EU are welcome to submit an application for funding, any offers will be subject to BBSRC approval and criteria.


1. C. Risi, F. Zhao, D. Castagnolo*, Chemo-Enzymatic Metathesis/Aromatization Cascades for the Synthesis of Furans: Disclosing the Aromatizing Activity of Laccase/TEMPO in Oxygen-Containing Heterocycles, ACS Catal. 2019, 9, 7264-7269.

2. K. Lauder, A. Toscani, Y. Qi, J. Lim, S. J. Charnock, K. Korah, D. Castagnolo*, Photo-biocatalytic one-pot cascades for the enantioselective synthesis of 1,3-mercaptoalkanol volatile sulfur compounds. Angew. Chem., Int. Ed. 2018, 57, 5803-5807. (IF.12.1)

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