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Design and use of de novo cascades for the biosynthesis of new benzylisoquinoline alkaloids

Wang, Yu, Tappertzhofen, Nadine, Méndez-Sánchez, Daniel, Bawn, Maria, Lyu, Boyu, Ward, John M. and Hailes, Helen C. 2019. Design and use of de novo cascades for the biosynthesis of new benzylisoquinoline alkaloids. Angewandte Chemie International Edition 58 (30) , pp. 10120-10125. 10.1002/anie.201902761

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The benzylisoquinoline alkaloids (BIAs) are an important group of secondary metabolites from higher plants and have been reported to show significant biological activities. The production of BIAs through synthetic biology approaches provides a higher‐yielding strategy than traditional synthetic methods or isolation from plant material. However, the reconstruction of BIA pathways in microorganisms by combining heterologous enzymes can also give access to BIAs through cascade reactions. Most importantly, non‐natural BIAs can be generated through such artificial pathways. In the current study, we describe the use of tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six non‐natural alkaloids, in cascades from l‐tyrosine and analogues.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Publisher: Wiley
ISSN: 1433-7851
Funders: UCL (Dean's Prize), BBSRC, EPSRC
Date of First Compliant Deposit: 18 March 2021
Date of Acceptance: 17 May 2019
Last Modified: 06 Oct 2021 16:09

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