BSc Chemistry University of California Santa Cruz
PhD Chemistry University of California San Diego
Department of Pharmacy, National University of Singapore
18 Science Drive 4, Singapore 117543
Tel: +65 6601 2495
Fax: +65 6679 1554
Research within the Morinaka group uses natural products as an exploratory platform for the identification of new small molecule drugs and enzymes that carry out chemically difficult transformations. The research conducted is multidisciplinary across both areas of chemistry (analytical, spectroscopy, synthesis, organic, medicinal) and biology (microbiology, genomics, bioinformatics, molecular biology, biochemistry). Two general approaches are used in the laboratory:
Since the genes encoding natural products are ‘clustered’ in bacteria they can be readily identified. Genome sequencing efforts have shown that only a small percent of gene clusters encoding natural products can be linked to an isolated and characterized natural product. This vast array of genetic information remains a huge repository for small molecule discovery. This genetic information will be ‘mined’ in a targeted approach to connect a gene cluster to bacterially produced natural products. These isolated natural products will be used for testing against various clinically relevant diseases.
Gene sequencing efforts have revealed a significant amount of genetic information with regard to natural products. However, there remain a portion of natural products with clinical potential and too complex for chemical synthesis for which the genes encoding their production have not been identified. These situations have arisen in complex microbial communities such as marine sponge microbiomes where the producing microorganism is not easily identified. Efforts here will be focused on new strategies for identifying gene clusters for clinically relevant natural products from complex microbial communities. Once genes of interest are identified they will be transferred to a heterologous host for functional validation and sustainable production of natural products.
Both of these approaches will allow the identification of new chemical entities that hopefully harbor new modes of action against antibiotic resistant strains of bacteria and new forms of chemotherapy. Along the way, we will uncover the biosynthetic machinery used to construct these fascinating molecules allowing us to manipulate these systems using synthetic biology and engineering to expand the structural diversity that Nature has already created.
Publication list is available here.