Dr. James C. Errey
University of Oxford
Chemistry Research Laboratory
Mansfield Road
Oxford, OX1 3TA, UK

james.errey@chem.ox.ac.uk

James Errey

I joined the Blanchard group in August 2003 following completion of my PhD with Rob Field at the Center for Carbohydrate Chemistry.  During the course of my PhD my work centered on the biosynthesis of sugar nucleotides involved in the cell wall synthesis of a number of pathogenic microorganisms. This work involved the a close collaboration with Jim Naismith at the University of St Andrews where I originally started my PhD before the group moved and Mike McNeil at Colorado State University.   Prior to this I had completed my masters and bachelors degree at the University of Kent under the guidance of Gary Robinson studying signal transduction in quorum sensing.

References

Vetting MW, Errey JC, Blanchard JS. (2008) " Rv0802c from Mycobacterium tuberculosis: the first structure of a succinyltransferase with the GNAT fold."
Acta Crystallogr Sect F Struct Biol Cryst Commun. 64(Pt 11):978-85

Tello M, Jakimowicz P, Errey JC, Freel Meyers CL, Walsh CT, Buttner MJ, Lawson DM, Field RA. (2006)
"Characterisation of Streptomyces spheroides NovW and revision of its functional assignment to a dTDP-6-deoxy-d-xylo-4-hexulose 3-epimerase."
Chem Commun (Camb). (10):1079-81.

Errey JC, Blanchard JS. (2006) "Functional Annotation and Kinetic Characterization of PhnO from Salmonella enterica."
Biochemistry. 45(9):3033-9.

Yang M, Proctor MR, Bolam DN, Errey JC, Field RA, Gilbert HJ, Davis BG. (2005) "Probing the breadth of macrolide glycosyltransferases: in vitro remodeling of a polyketide antibiotic creates active bacterial uptake and enhances potency."
J Am Chem Soc. 127(26):9336-7.

Errey JC, Blanchard JS. (2005) "Functional characterization of a novel ArgA from Mycobacterium tuberculosis."
J Bacteriol. 187(9):3039-44.

Errey JC, Mukhopadhyay B, Kartha KP, Field RA. (2004) "Flexible enzymatic and chemo-enzymatic approaches to a broad range of uridine- diphospho-sugars."
Chem Commun (Camb). (23):2706-7.

A. B. Merkel, L. L. Major, J. C. Errey, M. D. Burkart, R. A. Field, C. T. Walsh, J. H. Naismith (2004) "The position of a key tyrosine in dTDP-4-Keto-6-deoxy-D-glucose-5-epimerase (EvaD) alters the substrate profile for this RmlC-like Enzyme."
J. Biol. Chem. 279, 32684-32691 (PDF).

1) Oxidative Stress

Mycothiol is the major small molecule thiol found in Actinomyces (such as Mycobacterium tuberculosis) which is believed to play a key role in bacterial defense mechanisms against oxidative stress. I am interested in characterizing 2 of the enzymes in involved in the biosynthesis of mycothiol namely MshA (transferase) and MshC (ligase).

2) Acetyltransferases

3) Sugar nucleotide biosynthesis

Sugar nucleotides play are key players in a wide range of biological processes ranging from the functional fine tuning of monosaccharide building blocks and oligosaccharide biosynthesis to natural product syntheses and protein glycosylation/cell signaling. I am currently involved in the synthesis/studies of a variety of such sugar nucleotides which are of interest as:

Biotransformations

The chemical synthesis of sugar nucleotides is usually complex and can take a number of chemical steps. This can be dramatically shortened to just a few steps using an enzymatic or chemoenzymatic approach. Using a number of enzymes cloned and over expressed from E.coli I was able to synthesize a number of sugar nucleotides including UDP-galactofuranose a key sugar nucleotide involved in cell wall synthesis in Mycobacterium tuberculosis.

Galactofuranose biosynthesis

Some of the most successful anti-tuberculosis drugs have been targeted against the mycobacterial cell wall and with the information gather over the past 50 years relating to its structure, function and biogenesis this has provided a platform for the development of a new generation of anti-tuberculosis drugs. One of the strategies that has been used to try to accomplish this, is to target newly identified metabolic pathways that are essential for the bacteria to survive by target the enzyme(s) that are involved in the pathway, by using genetic, structural and biochemical data. One of the pathways that have been targeted is that of the pathway involving the formation of galactofuranose. If the enzyme involved in the conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) (UDP-Gal mutase) is inhibited then, as galactofuranose is not found in man, a selective target against the bacterium will hopefully be found. The aim of this study is to try to characterize the mechanism by which UDP-gal mutase catalyzes the reaction, involving the interconversion of UDP-Galp to UDP-Galf. This has involved the enzymatic synthesis of UDP-Galp and UDP-Galf derivatives to determine the substrate specificity of the enzyme and to probe the reaction mechanism.

Rhamnose biosynthesis

Thymidine diphosphate L-rhamnose is the precursor of L-rhamnose and is required for the virulence of a number of bacterial pathogens. dTDP-L-rhamnose is biosynthesized from glucose-1-phosphate and deoxythymidine triphosphate (dTTP) via a pathway involving four distinct enzymes. This pathway doesn't exist in humans and the enzymes involved in the biosynthetic pathway are potential targets for the design of new therapeutic agents.