BSc Chemistry University of California Santa Cruz PhD Chemistry University of California San Diego
Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore 18 Science Drive 4, Singapore 117543 Tel: +65 6601 2495 Fax: +65 6679 1554 Email: phambi@nus.edu.sg
Research Interest
Natural products or secondary metabolites derived from plants, animals and microorganisms play a key role in drug discovery and development. The majority of small-molecule drugs used in medicine are either the natural products themselves or their derivatives. Host organisms use natural products to confer advantages in their local environment for various functions including communication, attraction, signalling, and defence. We can repurpose these molecules as pharmaceuticals for the treatment of infectious diseases and cancer.
The overall goal of the Morinaka Lab is to identify, characterize, and utilize new posttranslational modifying enzymes from natural product pathways for the production of peptide-based therapeutics and biomaterials. Our lab uses a combination of bioinformatics and synthetic biology to identify pathways of interest and to create modified peptides, respectively. New peptide products are subjected to a combination of spectroscopic and chemical analysis to define their molecular structures. The purified products are then tested in a variety of bioassays relevant to infectious diseases.
The current focus of our group is on posttranslational modifying enzymes from the radical SAM superfamily. These enzymes catalyse diverse reactions and have led to a variety of bioactive peptides. The most recent work in the Morinaka lab unified the activity of several subfamilies of radical SAM enzymes in their ability to catalyse formation of three-residue cyclophanes. These enzymes termed 3-residue cyclophane forming enzymes (3-CyFEs) catalyse C(sp2)-C(sp3) bond formation and define the triceptide natural product family. Triceptides are encoded in diverse bacteria from terrestrial, marine, and animal microbiomes. We have a long term vision to exploit 3-CyFEs and triceptide gene clusters as a source for bioactive peptides.