Enzymology in the Post genomic era

The incredible biochemical feats of enzymes have often left chemical technologists in awe and envy. Yet, enzymes are products of the same evolutionary tinkering that has produced practically every other cellular component. Are there any general principles concerning their evolution, and, if yes, how do we glean them in the post-genomic era?  I present a synthetic picture of the investigation of my group in this regard. Firstly, I discuss the general tendencies in enzyme evolution and the issue of whether there are different temporal phases in which different catalytic activities were acquired by different protein folds. I also provide an empirical view of the differential accommodation of diverse catalytic activities by various protein folds and explore the issue of any obvious structural determinants of differential propensity for catalytic diversity. Thereafter, I consider the processes concerning the emergence of enzyme from non-enzymatic domains and vice-versa. To illustrate the divergent evolution of different catalytic mechanisms from similar active sites I use the case of acidic active site Rossmannoid domains. Here, I discuss how the emergence of certain peculiar structural elements termed the flap, the caps and squiggle allowed the emergence of the unique catalytic mechanisms of the HAD superfamily of phosphohydrolases. Moving on to convergent evolution, I show how very different structural scaffolds can support similar catalytic mechanisms and as an example of this principle present the discovery of a long elusive enzyme: the deoxyhypusine hydroxylase. Finally, in investigating comparative genomics of major enzyme superfamilies, I present evidence for the concept that the bacteria are the main “engines” of biochemical diversity and that the eukaryotes and archaea have *repeatedly* acquired activities invented by the bacteria readymade and utilized to them to achieve “difficult” biochemical adaptations rapidly.