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chemzymes
chemistry with enzymes
Research
Underexplored enzymatic transformations
Enzymes have, over the past few decades, evolved to valuable synthetic tools. Their unparalleled potential for catalyst-controlled selectivity and their ability to effect challenging transformations under mild conditions make them extremely powerful catalysts. Nonetheless, the current pool of well understood, robust and versatile enzymes is relatively small. Therefore, an overarching theme of my research is the exploration of sparsely charted space of enzymatic transformations.
Previously, a lot of my research was focussed on nucleoside phosphorylases, family of enzymes that (although they have been described in the literature more than 70 years ago) catalyze poorly understood thermodynamically controlled reactions. Our research derived general principles for the optimization of these systems based on a fundamental theoretical understanding. That subsequently enabled the synthesis of previously inaccessible nucleoside analogues (either bearing methylated sugars or selenonucleobases) in a highly predictable manner.
More recently, my focus has shifted to rather exotic archaeal ether synthases. These unusual enzymes perform challenging carbocation chemistry in a tremendously solvent-exposed active site. Our recent forays into this enzyme family revealed these biocatalysts to be promiscuous, tunable, insanely stable and extremely selective. However, we are only beginning to understand how they work and how we can employ them for useful chemistry.
Biocatalytic method development
Our understanding of enzymatic transformations is often limited by the amount of information we can gather about a given reaction system. Therefore, the development of efficient methodologies for the monitoring of enzymatic transformations is a constant area of interest in my research.
In the past, we have established a general method for the discontinous monitoring of nucleoside phosphorylase-catalyzed reactions, which resolved a lot of the problems with existing techniques and permitted us to address previously intractable problems. That method relies on spectroscopic differentiation of nucleosides and nucleobases as their anions. Building on the same principle, we have recently disclosed a highly versatile method for continuous high-throughput (pyro-)phosphate detection in biochemical assays, the PUB module. In the spirit of open science, we also reported our subsequent failures to further improve the sensitivity of that method by employing alternative assay reagents. Applications of those methods to contemporary biocatalytic problems as well as the development of further analytical methods are ongoing projects.
Most of my research has to do with biocatalysis; effecting chemical transformations with enzymes. I am interested in how enzymes work and how they can make synthetic chemistry easier. Along the way, I invent methods to help us answer these questions.
As biocatalysis is an inherently interdisciplinary field, that type of research spans different areas of the life sciences. Most projects include classical biochemistry (cloning, protein production and purification, enzyme kinetics...), analytical chemistry (UV, NMR and/or fluorescence spectroscopy, MS, chromatography...), physical chemistry (reaction equilibria, binding studies, Eyring-type analyses...), and organic chemistry (synthesis, purification, compound characterization...).
As such a high degree of interdisciplinary fails to characterize people by field, I would not consider myself a chemist or a biologist (although I, of course, do both chemistry and biology). Instead, I typically like to think in terms of areas of interest. Therefore, I do chemistry with enzymes and most of my research falls into the following two categories:
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