WISB Research Career Development Fellow
Identification of new halogenated synthetic, natural and non-natural compounds; and further exploitation and synthesis of these compounds are of extreme importance in this modern era. This is due to the profound role of organo halides as pharmaceuticals, agrochemicals and valuable synthons in various organic reactions. As an organic synthetic intermediate, halogenated molecules are of particular importance in many metal-catalyzed cross-coupling reactions. Nature has evolved a number of biocatalysts to regioselectively halogenate a diverse range of biosynthetic precursors and secondary metabolites, and this unexplored repertoire is ever growing. Biosynthetic halogenation can occur over simple to extremely complex ring structures of natural compounds and in some cases it initiates the formation of complex structures and scaffolds. These reactions often range from simple aromatic substitutions to complex stereoselective C-H functionalization and activation of remote carbon centers. These reliable, facile and cleaner biosynthetic routes have potential utility and greater demand over traditional nonenzymatic halogenation chemistry that requires deleterious reagents and lacks regio-control.
My research is focused on this challenging and highly multidisciplinary area that tackle, identify and exploit potential untapped and alternative sources of these biocatalysts. This will be attempted via the development of new synthetic/biosynthetic routes and plausible chemo-enzymatic approaches that can directly incorporate halogenases. The versatility and application of these methods when combined with existing natural product biosynthetic pathways will open up new modes of synthesizing building blocks and derivatives of many existing drug targets and APIs that are currently marketed. Another interesting application is to provide non-natural amino acids or its precursors with unique chemical or biophysical properties that can mimic naturally occurring (post-translational) or imposed modifications. This could be used for the production and optimization of artificial enzymes and for the development of therapeutic peptides by directed evolution, combinatorial/retrospective engineering and machine learning techniques. These approaches thus combine different aspects and research tools available from the fields of synthetic biology, enzymology, structural biology, biocatalysis, medicinal chemistry and organocatalysis.