Dehydrogenases are important components of numerous biochemical pathways. The catalyse redox reactions of numerous substrates and require cofactors such as NAD+ or NADP+. One example is the Glucose-6-phosphate dehydrogenase (G6PD) that forms part of the pentose phosphate pathway that is essential for a variety of reasons. G6PD is used in the production NADPH that is necessary for dealing with oxygen stress. As a consequence people with defective G6PD show reduced susceptibility to malaria, but can also have an adverse reaction to some of the more common anti-malaria drugs. Apart from its medical importance, G6PD is of some commercial importance as it is used to generate NADPH for numerous applications. A high throughput screen would be useful to identify G6PD mutants with enhanced activity and stability – our preliminary results indicate that this may indeed possible. Mutant proteins identified in this manner may be of some commercial value and could also be studied to obtain functional information and to identify factors important for stability. Such a screen might be modified to produce a field test to identify people with defective G6PD.
The high throughput screen being devised for G6PD monitors the production of NADPH or NADH and can therefore be used to detect activity in a variety of dehydrogenases. Numerous applications for this screen are clearly possible.