Multienzyme One-Pot Cascades Incorporating Methyltransferases for the Strategic Diversification of Tetrahydroisoquinoline Alkaloids.
alkaloids
biocatalysis
methyltransferases
one-pot cascades
regioselectivity
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
16 08 2021
16 08 2021
Historique:
revised:
19
05
2021
received:
31
03
2021
pubmed:
9
6
2021
medline:
9
6
2021
entrez:
8
6
2021
Statut:
ppublish
Résumé
The tetrahydroisoquinoline (THIQ) ring system is present in a large variety of structurally diverse natural products exhibiting a wide range of biological activities. Routes to mimic the biosynthetic pathways to such alkaloids, by building cascade reactions in vitro, represents a successful strategy and can offer better stereoselectivities than traditional synthetic methods. S-Adenosylmethionine (SAM)-dependent methyltransferases are crucial in the biosynthesis and diversification of THIQs; however, their application is often limited in vitro by the high cost of SAM and low substrate scope. In this study, we describe the use of methyltransferases in vitro in multi-enzyme cascades, including for the generation of SAM in situ. Up to seven enzymes were used for the regioselective diversification of natural and non-natural THIQs on an enzymatic preparative scale. Regioselectivites of the methyltransferases were dependent on the group at C-1 and presence of fluorine in the THIQs. An interesting dual activity was also discovered for the catechol methyltransferases used, which were found to be able to regioselectively methylate two different catechols in a single molecule.
Identifiants
pubmed: 34101966
doi: 10.1002/anie.202104476
pmc: PMC8457072
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18673-18679Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R021643/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N01877X/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 219857/Z/19/Z
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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