A Cryptic Plant Terpene Cyclase Producing Unconventional 18- and 14-Membered Macrocyclic C
Leucosceptrum canum
enzyme engineering
immunosuppressive activity
macrocyclic terpenoids
sesterterpene synthase
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:
22 11 2021
22 11 2021
Historique:
revised:
20
09
2021
received:
13
08
2021
pubmed:
29
9
2021
medline:
16
12
2021
entrez:
28
9
2021
Statut:
ppublish
Résumé
A versatile terpene synthase (LcTPS2) producing unconventional macrocyclic terpenoids was characterized from Leucosceptrum canum. Engineered Escherichia coli and Nicotiana benthamiana expressing LcTPS2 produced six 18-/14-membered sesterterpenoids including five new ones and two 14-membered diterpenoids. These products represent the first macrocyclic sesterterpenoids from plants and the largest sesterterpenoid ring system identified to date. Two variants F516A and F516G producing approximately 3.3- and 2.5-fold, respectively, more sesterterpenoids than the wild-type enzyme were engineered. Both 18- and 14-membered ring sesterterpenoids displayed significant inhibitory activity on the IL-2 and IFN-γ production of T cells probably via inhibition of the MAPK pathway. The findings will contribute to the development of efficient biocatalysts to create bioactive macrocyclic sesterterpenoids, and also herald a new potential in the well-trodden territory of plant terpenoid biosynthesis.
Identifiants
pubmed: 34580976
doi: 10.1002/anie.202110842
doi:
Substances chimiques
Immunosuppressive Agents
0
Interleukin-2
0
Macrocyclic Compounds
0
Terpenes
0
Interferon-gamma
82115-62-6
Alkyl and Aryl Transferases
EC 2.5.-
terpene synthase
EC 2.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
25468-25476Subventions
Organisme : National Natural Science Foundation of China
ID : 21937006, 31525005, 31770390, 31770340 and 31800298
Organisme : Yunnan Key Research and Development Program
ID : 2019ZF011-2
Informations de copyright
© 2021 Wiley-VCH GmbH.
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