Greener Chemistry with Enzymes: Unlocking the Synthesis of Challenging Cyclopropane Motifs through Biocatalysis

Project ID: 2531bd1637

(You will need this ID for your application)

Research Theme: Manufacturing The Future

Research Area(s): Catalysis
Synthetic Organic Chemistry

UCL Lead department: Chemistry

Project Summary:

The cyclopropane ring is an important structural motif found in many pharmaceutical compounds and serves as a versatile building block in chemical synthesis. Despite numerous synthetic strategies, current methods often face significant limitations in selectivity and sustainability, frequently relying on hazardous or potentially explosive reagents.

This project aims to develop new biocatalytic strategies for the synthesis of cyclopropanes through the identification, characterization, and optimization of novel enzymes. The focus will be on cyclopropane synthases and 2-oxoglutarate/Fe(II)-dependent dioxygenases, which naturally catalyze cyclopropanation reactions. The PhD candidate will work on identifying, expressing, and purifying wild-type enzymes, as well as bioengineering them to serve as efficient and selective biocatalysts for targeted cyclopropanation reactions.

The student will receive extensive multidisciplinary training spanning protein expression and purification, biocatalytic screening, LC-MS/GC-MS analysis, synthetic chemistry, and enzyme engineering. The project will be conducted entirely at UCL’s Manufacturing Futures Lab (https://www.ucl.ac.uk/manufacturing-futures-lab), a state-of-the-art interdepartmental research hub equipped with cutting-edge instruments, including HPLC, LC-MS, GC-MS, NMR, and robotic systems for automated mutagenesis and enzyme screening. The project will be supervised by Prof. Daniele Castagnolo.

Applicants should hold, or be expecting to achieve, a first or upper second-class Honours degree (or equivalent) in organic chemistry, medicinal chemistry, molecular biology, biochemical engineering, or a closely related discipline.

Interested candidates should contact Prof. Daniele Castagnolo (d.castagnolo@ucl.ac.uk) with a degree transcript and a motivation letter expressing interest in the project. Informal inquiries are welcomed.