Enzymatic Investigations in Gentamicin C Biosynthesis
Lead Research Organisation:
University of Cambridge
Department Name: Chemistry
Abstract
Theme: Industrial Biotechnology and Bioenergy
The inevitable approach of the post-antibiotic era has focussed attention on the revamp of established antibacterial agents in order to attain more robust variants. Re-engineering the biosynthetic pathway of a natural product-derived antibiotic is an attractive alternative to semisynthetic approaches; a prerequisite for this is cognizance of the complete biosynthetic
enzymology.
This project will endeavour to explore the substrate specificity of the aminotransferases GenB1, GenB2, GenB3 and GenB4
involved in the distinctive 3',4'-bisdehydroxylation process in gentamicin biosynthesis, by functional enzyme studies using
substrate analogs. This would enable efforts to rationally manipulate the enzymatic transformations which is a prerequisite
for the task of redirecting the course of the biosynthetic pathway to obtain a defined composition of end-product. Likewise, engineering the substrate specificity of the dehydrogenase GenQ will need to be undertaken to contribute to the accomplishment of such an aim. Previous studies concerning the JI-20B/JI20Ba epimer pair - on the determination of configuration at the chiral C-6 position - will also be concluded.
The inevitable approach of the post-antibiotic era has focussed attention on the revamp of established antibacterial agents in order to attain more robust variants. Re-engineering the biosynthetic pathway of a natural product-derived antibiotic is an attractive alternative to semisynthetic approaches; a prerequisite for this is cognizance of the complete biosynthetic
enzymology.
This project will endeavour to explore the substrate specificity of the aminotransferases GenB1, GenB2, GenB3 and GenB4
involved in the distinctive 3',4'-bisdehydroxylation process in gentamicin biosynthesis, by functional enzyme studies using
substrate analogs. This would enable efforts to rationally manipulate the enzymatic transformations which is a prerequisite
for the task of redirecting the course of the biosynthetic pathway to obtain a defined composition of end-product. Likewise, engineering the substrate specificity of the dehydrogenase GenQ will need to be undertaken to contribute to the accomplishment of such an aim. Previous studies concerning the JI-20B/JI20Ba epimer pair - on the determination of configuration at the chiral C-6 position - will also be concluded.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011194/1 | 01/10/2015 | 31/03/2024 | |||
| 1804949 | Studentship | BB/M011194/1 | 01/10/2016 | 08/02/2019 | Emma Thompson |