Tai Ng Rose Hills
Towards the Biosynthesis of Physostigmine
Streptomyces is a large genus of actinobacteria well known for their secondary metabolism, producing a large array of antibacterial, antifungal, and antiparasitic drugs. The compound of interest in this project is physostigmine, produced by Streptomyces griseofuscus. Physostigmine is a tryptophan-derived alkaloid that reversibly inhibits acetylcholinestrase. It is a candidate drug for treating numerous neurological disorders such as Alzheimer’s disease, myasthenia gravis, glaucoma, and orthostatic hypotension. Studying the biosynthesis of physostigmine can provide insight into the biosynthesis of a large family of alkaloids with the unique pyrroloindole skeleton. Furthermore, understanding the key enzymes responsible for the biosynthesis will also allow the engineering of physostigmine-like analogs from modified tryptophan substrates.