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Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids
Author(s) -
Wang Yu,
Tappertzhofen Nadine,
MéndezSánchez Daniel,
Bawn Maria,
Lyu Boyu,
Ward John M.,
Hailes Helen C.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201902761
Subject(s) - benzylisoquinoline , biosynthesis , chemistry , enzyme , biochemistry , stereochemistry , combinatorial chemistry , computational biology , biology
Abstract 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.