Functionalization of readily available aromatic compounds such as benzene or naphthalene requires harsh conditions. Among other modifications, Nature makes use of reversible carboxylation of these compounds through action of the UbiD enzyme (1). We have recently demonstrated how the UbiD enzyme in concert with UbiX achieves this remarkable reaction (2,3). In addition, we have recently determined the structure of the first CAR enzyme, a carboxylic acid reductase with broad substrate specificity (4). Combination of both enzyme activities (ie UbiD/X and CAR) should allow for convertion of aromatic compounds into high value products such as aldehydes or amides via the carboxylic acid intermediate in vivo. To this end, we seek to study a range of UbiD/X and CAR enzymes, to explore the scope for aromatic functionalization using combinatorial combination of these proteins. Research will be carried out at the MIB (www.mib.ac.uk), providing state-of-the art infrastructure for protein biochemistry, enzyme characterization, structural biology and synthetic biology.
You will be able to engage with various disciplines, with an emphasis on enzyme characterization (including structural biology/protein crystallography) and evolution, in addition to analytical chemistry, organic chemistry and modeling, providing a multidisciplinary training in the groups of David Leys, Nick Turner and Neil Dixon. This project would suit individuals interested in future careers in enzymology/structural biology, biotechnology, biocatalysis and bioprocessing.
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
Contact for further Information
For further information, please contact David Leys ([email protected]
This project is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships
1. Marshall et al. (2017) The UbiX-UbiD system: The biosynthesis and use of prenylated flavin (prFMN).Arch. Biophys Biochem., in press https://doi.org/10.1016/j.abb.2017.07.014
2. Payne, et al. (2015) New cofactor supports reversible decarboxylation of -unsaturated acids via 1,3-dipolar cycloaddition chemistry. Nature 522, 497–501
3. White, et al. (2015) UbiX is a flavin prenyltransferase required for bacterial ubiquinone biosynthesis. Nature 522, 502–507
4. Galoth, et al. (2017) Structures of carboxylic acid reductase reveal domain dynamics underlying catalysis. Nature chemical biology 13, 975-981