Funded PhD Studentship
How do non-metal dioxygenases activate substrates?
Supervisors
Dr Sam de Visser — School of Chemical Engineering & Analytical Science
Dr Steve Rigby — Manchester Centre for Biophysics and Catalysis (MCBC)
Project Aims
Recently, two unique enzymes were identified that catalyze an oxygenation reaction without the use of metal co-factors, namely Arthrobacter nitroguajacolicus Rü61a 1-H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) and Pseudomonas putida 33/1 1-H-3-hydroxy-4-oxoquinoline 2,4-dioxygenase (QDO). All known oxygen utilizing enzymes in nature use a transition metal active site containing either Fe, Mn or Cu, to transfer one or two oxygen atoms of O2 to a substrate. These are vital processes for human health and include DNA base repair mechanisms and the biodegradation of xenobiotics. In nature, molecular oxygen requires considerable energy to catalyze an oxygenation reaction, therefore, these non-metal dioxygenases clearly have a unique mechanism in place to assist the reactions, although the intricate details of the mechanism are currently unknown. Moreover, the lack of expensive and toxic metals in the reactivity would make their industrial biotechnological applications more interesting. In order to gain insight into this unique mechanism and test its biotechnological applications, we aim to do a combined high-level computational and electron paramagnetic resonance (EPR) study on the mechanism and characterisation of short-lived intermediates in the catalytic cycle. We will compare the activity and substrate selectivity of metal and non-metal dioxygenases and reveal their differences and comparisons.
Entry Requirements
Applicants must have obtained, or be about to obtain, a first or upper second class UK honours degree, or equivalent qualifications gained outside the UK, in an appropriate area of science or technology.
The studentship provides funding for fees and stipend at the Research Council UK rate and are available to eligible UK and EU nationals (due to funding criteria, EU nationals MUST have resided in the UK for three years prior to commencing the studentship). EU applicants that have not resided in the UK for three years prior to commencing the studentship, are eligible for a ‘fees only’ studentship.
Informal enquiries may be directed to Dr Sam de Visser sam.devisser@manchester.ac.uk
See: The BBSRC Doctoral Training Partnership (DTP) Studentships How to apply page for details of the application process.
Applications deadline: 12th March 2012.