Exploring chemical versatility within the tautomerase superfamily
|PhD ceremony:||Mr J.B. Baas|
|When:||December 22, 2014|
|Supervisors:||prof. dr. G.J. (Gerrit) Poelarends, prof. dr. W.J. (Wim) Quax|
|Where:||Academy building RUG|
|Faculty:||Science and Engineering|
Bert-Jan Baas has investigated how evolution works at the molecular level of enzymes, being one of the key components of living cells. The theory of evolution is usually described at the level of organisms and populations as a whole. Evolution, however, takes place at a far more fundamental level in the cells that make up an organism.
Baas has investigated how a family of cis-3-chloroacrylate dehalogenases, enzymes that degrade a man-made compound, may have evolved within the context of the tautomerase superfamily. Surprisingly, he found that several tautomerases in this superfamily exhibit low-level promiscuous dehalogenase activity, whereas the cis-3-chloroacrylate dehalogenases possess low-level tautomerase activity. These shared promiscuous activities suggest that these dehalogenases divergently evolved from tautomerases and that catalytic promiscuity played a crucial role in this process. Hence, low-level promiscuous activities of existing enzymes may function as starting points to evolve new enzymes, where the promiscuous activity has been enhanced to a useful level.
In addition, the diverse chemistry catalyzed by members of the tautomerase superfamily was investigated. This has led to the discovery of a rare cofactor-independent enzyme that catalyzes a direct reaction between molecular oxygen and an organic substrate, an activity that was unknown to occur in this superfamily. This highlights the extraordinary chemical versatility of enzymes belonging to the tautomerase superfamily, and questions us what other catalytic abilities are still out there, waiting to be discovered.