Norcoclaurine Synthases: Expanding Applications to Novel Alkaloid Scaffolds Through Enzyme Engineering and Structural Studies

Norcoclaurine synthase is a Pictet-Spenglerase which performs the first committed step in the biosynthetic pathway to alkaloids including morphine. Recently we have used NCSs in biocatalytic reactions with aldehydes and ketones and carried out mechanistic studies supported by X-ray crystal structures. This project will investigate the generation of novel NCSs that significantly expands their capability to generate amine heterocyclics and other regioisomers. Also, NCSs that can accept bulky amine or non-activated substrates and change the stereoselectivity at C-1. New enzymes will be cloned and NCS mutants will be generated via rational design aided by x-ray crystallographic studies.