Alex Ascham

Engineering ATP-Grasp Enzymes for the Preparation of Pharmaceutical Amides

About me

I completed my MChem Chemistry at the University of York where I spent my final year using bioelectrochemistry to study cellulose degrading enzymes for the refinery of biomass. This project introduced me to the engineering and application of enzymes in industry, as well as teaching me a completely different practical skill set from traditional chemistry. I am excited to undertake a PhD project that allows me to gain experience in structural and molecular biology, as well as organic and analytical chemistry.

My research

Amide bond synthesis is the single most common reaction in the pharmaceutical industry but largely relies upon atom inefficient coupling reagents and toxic solvents. Biosynthesis provides a more sustainable route to amides, using natural amide bond forming enzymes. A continuing area of research in the group is the use of adenylating enzymes, which use ATP to activate the carboxylic acid substrate, generating an acyl adenylate intermediate. My project focuses on ATP-grasp enzymes, typified by D-Ala-D-Ala ligase, part of the peptidoglycan biosynthetic pathway. Using ATP as a cofactor, these enzymes generate a simpler acyl phosphate intermediate, which is attacked by a nucleophilic amine substrate. While these enzymes have been used to synthesis oligopeptides, they have not been applied to the synthesis of amides from non-canonical amino acids. Development of a novel class of enzyme for the production of neutral amides could increase the variety and simplicity of pharmaceutically relevant amide biosynthesis.