Em Prof J R Guest FRS
Professor Guest trained as a biochemist and since 1965 has pioneered the use of bacterial genetics, gene cloning, DNA sequencing, site-directed mutagenesis, chromosomal gene replacement (reverse genetics) and metabolic engineering, in Sheffield. Using Escherichia coli as a model organism he identified genes that are essential for aerobic and anaerobic respiratory metabolism. He made detailed molecular characterisations of the structure function and expression of many components of the citric acid cycle and related aerobic and anaerobic respiratory pathways. He likewise discovered and characterised an oxygen-sensing transcriptional regulator (FNR) that serves as a global switch for controlling the metabolic response to anaerobiosis.
Current interests include:
- The relative roles physiological significance of two routes of aerobic pyruvate oxidation in E. coli mediated by the pyruvate dehydrogenase complex and pyruvate oxidase.
- The physiological consequences and structural implications of domain engineering in the pyruvate dehydrogenase multi-enzyme complex.
- The dual roles of two citric acid cycle enzymes, aconitase A and B, as both metabolic catalysts and RNA-binding proteins that mediate a novel oxidative-stress responding and rapidly reacting, post-transcriptional mechanism of regulating gene expression.
Abdel-Hamid, A.M., Attwood, M.M. and Guest, J.R. (2001). Pyruvate oxidase contributes to the aerobic growth efficiency of Escherichia coli. Microbiology 147, 1483-1498. Arjunan, P., Nemeria, N., Brunskill, A., Chanrasekhar, K., Sax, M., Yan, Y., Jordan, F., Guest, J.R. and Furey, W. (2002). Structure of the pyruvate dehydrogenase multienzyme complex E1 component from Escherichia coli at 1.85 Å resolution. Biochemistry 41, 5213-5221. Green, J., Scott, C. and Guest, J.R. (2001). Functional versatility in the CRP-FNR superfamily of transcription factors: FNR and FLP. Adv. Microb. Physiol. 44, 1-34. Guest, J.R., Abdel-Hamid, A.M., Auger, G.A., Cunningham, L., Henderson, R.A., Machado, R.S. and Attwood, M.M. (2003). Physiological effects of replacing the PDH complex of E. coli by genetically engineered variants or by pyruvate oxidase. In Thiamine: Catalytic Mechanisms and Role in Normal and Disease States, ed by M.S. Patel and F. Jordan, pp 389-407. Marcel Dekker Inc, New York.