Novel Biocatalysts for Improved Routes to an Active Pharmaceutical Ingredient

Lead Research Organisation: University of Manchester
Department Name: Chemistry

Abstract

The use of enzymes to catalyse reactions is a well established technique used in modern organic chemistry as the use of biological catalysts can install unique and exquisite stereochemistry and regiochemistry into a synthetic route. This project will explore the development of two enzymes that catalyse important bond forming reactions in the synthesis of an Active Pharmaceutical Ingredient and their suitability for use as industrial biocatalysts.

Technical Summary

This project will evaluate the feasibility of replacing the current complex chemical syntheses of key intermediates towards Sofosbuvir (Sovaldi), an important drug used in the treatment of Hepatitis C, with biocatalytic steps, offering a shorter route to the product, with enhanced efficiency, economy, and environmental performance. The project will utilise the expertise of the University of Manchester in enzyme discovery and engineering to provide the new catalysts, and the manufacturing expertise of Dr. Reddy's to assess the feasibility of using these catalysts on an industrial scale.

Planned Impact

As described in the proposal submitted to IUK

Publications

10 25 50
 
Description We explored the use of an aldolase enzyme for the synthesis of sugar structures that are incorporated into drug molecules use to treat Hepatitis C. The new methodology would significantly reduce the number of steps required for the synthesis and lead to potential production cost savings that could be passed on to the consumer.
Exploitation Route Future enzyme development based upon or feasibility study should facilitate the necessary technology development to fully realise the original objectives.
Sectors Manufacturing, including Industrial Biotechology

 
Description IB Catalyst Feasibility Project 
Organisation Chirotech Technology
Country United Kingdom 
Sector Private 
PI Contribution Collaborative research project funded through the IB Catalyst scheme. We have contributed intellectual input to the project by proposing a novel route to an advanced pharmaceutical intermediate. Access to this API is a cost effective way will allow Chirotech to compete with the established production processes.
Collaborator Contribution Chirotech will help to provide training in specialised chemical synthetic methods via a series of technology transfer events.
Impact The project commenced on the 1st of February 2016 so there are no outputs yet.
Start Year 2016
 
Description Manchester Institute of Biotechnology open day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact The annual A-Level Open Day was run for the 5th time with the overall aim of raising the profile of biotechnology and its feeder subjects among those considering university and changing the perception of scientists among teenagers and young adults. The day was filled with lab tours, informative talks and interactive demonstrations of various aspects of the research in the institute.

We have received requests for Nuffield Summer Placements of students.
Year(s) Of Engagement Activity 2013,2014,2015,2016
URL http://www.mib.ac.uk/newsandevents/publicengagement/