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Synthetic approaches towards designer biological UV filters

Principal supervisor: Professor John McCarthy, School of Life Sciences

Second supervisor: Dr Christophe Corre, School of Life Sciences

Industry partner: Croda Europe Ltd

Project Title: Synthetic approaches towards designer biological UV filters

University of registration: University of Warwick

Project outline:

This project will explore the development and application of a novel synthetic biology strategy to optimise biosynthetic pathway performance using advanced biodesign methods combined with automation. While the strategy is intended to be broadly applicable, we will focus on one, industrially important, pathway as a proof-of-principle system in order to refine and demonstrate the approach.

Mycosporine-like amino acids (MAAs) are small (<400 Da), colourless, and water-soluble molecules characterized by their ability to absorb UV. They are amino acid substituted cyclohexenimine ring conjugated molecules with over 30 different structures known in nature. This structural variation leads to compounds that absorb UV at different wavelength-maxima and that may increase the efficacy of existing sun-screen formulations.

In nature, MAAs are produced at low yields in generally non-tractable organisms. Therefore, the exciting challenge here is to engineer an amenable production host such as Saccharomyces cerevisiae so that it generates comparatively high yields of the required products. Additionally, production of MAAs poses systems challenges requiring coordinated heterologous gene expression and metabolic precursor availability both in central carbon metabolism and the intracellular amino acid pool.

Recent research has identified many of the MAA biosynthetic pathways providing the foundation for the project and meaning that much of the enzyme discovery work has been done. The project will accordingly focus on combinatorial assembly of different enzyme variants together with different-strength (synthetic) expression signals in order to create enhanced-yield pathways. Synthetic regulatory components will be developed and utilised to help optimise the performance of engineered strains. Computational modelling will be utilised, where appropriate, to enhance pathway optimisation.

The industrial research partner is the leading global supplier of inorganic based TiO2 and ZnO dispersions for use in sunscreen. The company has developed novel patented solutions to allow the formulation of aesthetically pleasing, high SPF, high UVA products. A recent shift in the use of UV actives in daily skincare products has brought with it new expectations to formulate high SPF, light skin feeling products. Changes to regulations stipulating the requirement for high UVA protection adds additional complexity to this challenge. As a result, there is a strong requirement for highly effective, photostable organic UV absorbers, especially in the UVA region of the electromagnetic spectrum. This project provides a new route to developing productive processes for making a range of MAAs.

The project will involve the use of techniques in molecular biology, robotics, and gene expression analysis, as well as, where appropriatre, computational modelling. The appointed researcher will have access to the outstanding facilities offered by the Warwick Integrative Synthetic Biology centre .

Contact: Professor John McCarthy, University of Warwick