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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.
Disciplines and Techniques
Project supervisor/s
Professor Helen Hailes
Helen is interested in developing sustainable synthetic methods using biocatalysts in single-step reactions, multi-step cascades and performing reactions in water.
University College London
Professor Nick Keep
Nicholas's interests are in macromolecular crystallography and, in collaboration with colleagues at the Institute of Structural and Molecular Biology (ISMB), single particle electron microscopy and NMR to understand biological function.
Birkbeck University of London
References
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FEBS J, 282, 1837
2015
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Biochemistry, 40, 5269
2017
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Nature Commun., , 8, 14883
2017
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Chem. Commun., 54, 1323
2018
https://doi.org/10.1002/anie.201902761
Chem. Int. Ed.,
2019