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Design and use of de novo cascades for new benzylisoquinoline alkaloid biosynthesis

Hailes, H; Ward, J; Wang, Y; Tappertzhofen, N; Mendez-Sanchez, D; Bawn, M; Lyu, B; (2019) Design and use of de novo cascades for new benzylisoquinoline alkaloid biosynthesis. Angewandte Chemie , 58 (30) pp. 10120-10125. 10.1002/anie.201902761. Green open access

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Abstract

The benzylisoquinoline alkaloids (BIAs) are an important group of higher plant secondary metabolites, which have been reported to show significant pharmaceutical activities. The production of BIAs via synthetic biology approaches provides a higher yielding strategy compared to traditional synthetic methods and plant isolation methods. However, the reconstruction of BIAs pathways in microorganisms combining heterologous enzymes can also give access to BIAs via cascade reactions. Most importantly, non‐natural BIAs can be generated through such artificial pathways. In the current study, we describe new 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.

Type: Article
Title: Design and use of de novo cascades for new benzylisoquinoline alkaloid biosynthesis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/anie.201902761
Publisher version: https://doi.org/10.1002/anie.201902761
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Biocatalysis, benzylisoquinoline alkaloids, norcoclaurine synthase, enzyme cascades
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10074317
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