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Research: Pathway elucidation
A large part of what we do centres on elucidating the biosynthetic pathways of the cofactors of interest to us, and then following this up with detailed mechanistic, kinetic and structural studies of the particular enzymes involved. For example, CoA is biosynthesized in five steps as shown in the figure, and although the pathway has now been established in most organisms, some interesting questions still remain. For example, our group was the first to characterize a new type of pantothenate kinase enzyme (later dubbed Type III PanK, or PanK-III) that is mainly found in pathogenic bacteria. We have shown that these Type III PanKs can easily be differentiated from their well-known Type I and Type II counterparts based on both biochemical and structural studies. More recently we were intimately involved in a study conducted by our collaborators in Spain (Prof. Joaquín Ariño at UAB in Barcelona) that characterized a heterotrimeric protein as the phosphopantothenoylcysteine decarboxylase (PPCDC) enzyme in yeast.
Currently we are also exploring the enzymes in the mycothiol biosynthetic pathway of M. tuberculosis, as this organism is dependent on this low molecular weight thiol to maintain its intracellular redox balance.
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