Enzymes for Sustainable Amide Synthesis Under Aqueous Conditions for Pharmaceutical Applications

Description

A PhD studentship is available to work on a multidisciplinary project led by Professor Andrew Carnell on the discovery and development of enzymes for application in the sustainable synthesis of amides under aqueous conditions.

Amide bond formation is recognised as the most frequently used reaction in the synthesis of pharmaceuticals. Carboxylic acids are generally activated as acid chlorides or anhydrides prior to reaction with amines.  Alternatively, a wide range of coupling reagents can be used. However, these approaches use toxic materials or require difficult separations and are not atom economic.

Biocatalytic methods have emerged as a complementary approach, with lipases most often used for the synthesis of esters and also amides, although the use of organic solvents to minimise competing hydrolysis reduces sustainability. The ability to catalyse acyl transfer reactions to synthesise amides in aqueous media is extremely desirable and makes the amidation compatible with other enzyme reactions.

In this project you will discover and develop a new class of hydrolase enzymes that have promiscuous activity for catalysing amide bond formation with high efficiency under aqueous conditions. This will be based on several new enzymes that we have recently identified. You will use a combination of computational predictions and experimental work to develop robust and scalable biocatalysts and demonstrate their use in synthesis.

This multi-disciplinary project will combine biocatalysis, synthetic chemistry, molecular biology, and computational biology.  You are not expected to have prior experience in all these areas and you will receive training in world class research environment with access to state-of-the-art facilities for biocatalysis (Professor Carnell, Department of Chemistry), computational Biology (Professor Rigden, Institute of Systems, Molecular and Integrative Biology) and enzyme production and screening (Dr Salcedo-Sora, Liverpool GeneMill). You will have the opportunity to present your work at regular interdisciplinary research group meetings and at national conferences.

You should hold or expect to hold a first class or high 2:1 or equivalent in chemistry (MChem), biochemistry or molecular biology or related (Masters or BSc). Informal enquiries can be made to Professor Andrew Carnell (acarnell@liverpool.ac.uk).

Useful links:

1, Carnell Group: https://www.liverpool.ac.uk/people/andrew-carnell

2. Rigden Group: https://www.liverpool.ac.uk/people/daniel-rigden
3. Liverpool GeneMiIll: https://www.liverpool.ac.uk/research/facilities/genemill/

How to Apply:  Formal applications should be made to How to apply for a PhD programme - University of Liverpool quoting reference CCPR130.  Candidates will be evaluated as applications are received, and the position may be filled before any deadline if a suitable candidate is identified.

This position is available immediately.