Chemoenzymatic Synthesis of Natural Products

Natural products are structurally interesting molecules (metabolites) produced in nature by organisms such as bacteria, fungi and plants. The unique scaffolds of these molecules often result in interesting biological activities that act as effective agents in the treatment of human disease. Studies have shown that ~40% of new approved drugs are natural products or natural product derivatives. These data emphasise the importance of natural product discovery and derivatisation. The pharmaceutical application of natural products is often underexplored as they are commonly isolated in sub-milligram quantities from their natural source and can be hard to access with traditional synthetic methods. The incorporation of enzymes in organic synthesis can overcome these issues with clear economic and environmental benefits. The discovery, characterisation, and exploitation of key biosynthetic enzyme classes as biocatalysts will ensure enhanced access to complex, bioactive chemical scaffolds in a greener, more environmentally benign manner. The ability for these reactions to be run in mild reaction conditions without the need for wasteful protection/deprotection steps, affords a more step economic synthetic approach to the manufacture of pharmaceuticals, agrochemicals, and other useful molecules. Key interests in the Murray Lab focus on the chemistry and biology of natural products, including: – Discovery of new natural products and investigating their biosynthesis in nature – Investigations of unusual biosynthetic enzymes and exploring their potential as biocatalysts – Harnessing enzymes to achieve chemoenzymatic synthesis of bioactive natural products Current projects within the lab focus on biologically active natural products including anti-cancer and anti-bacterial agents produced by bacteria. This research is positioned at the interface of biochemistry and chemistry and will leverage the powerful reactivity and selectivity of enzymes to access natural products and their analogues. This work will span a variety of disciplines including biochemistry, enzymology, structural biology, computational biology (bioinformatics, protein structure prediction), and synthetic organic chemistry (chemical synthesis and structural characterization using NMR and mass spectrometry). We are excited to mentor honours students who are interested in the above techniques and wish to pursue science in an inclusionary and interdisciplinary space. Projects can be tailored to match student’s specific interests.