Discovering Dynamic Plant Enzyme Complexes in Yeast for Kratom Alkaloid Pathway Identification.
Biosynthesis
Monoterpene Indole Alkaloids
Natural Products
Pathway Discovery
Plant Enzymes
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:
18 09 2023
18 09 2023
Historique:
received:
06
06
2023
pmc-release:
18
09
2024
medline:
15
9
2023
pubmed:
7
8
2023
entrez:
7
8
2023
Statut:
ppublish
Résumé
Discovering natural product biosynthetic pathways of medicinal plants is challenging and laborious. Capturing the coregulation patterns of pathway enzymes, particularly transcriptomic regulation, has proven an effective method to accelerate pathway identification. In this study, we developed a yeast-based screening method to capture the protein-protein interactions (PPI) between plant enzymes, which is another useful pattern to complement the prevalent approach. Combining this method with plant multiomics analysis, we discovered four enzyme complexes and their organized pathways from kratom, an alkaloid-producing plant. The four pathway branches involved six enzymes, including a strictosidine synthase, a strictosidine β-D-glucosidase (MsSGD), and four medium-chain dehydrogenase/reductases (MsMDRs). PPI screening selected six MsMDRs interacting with MsSGD from 20 candidates predicted by multiomics analysis. Four of the six MsMDRs were then characterized as functional, indicating the high selectivity of the PPI screening method. This study highlights the opportunity of leveraging post-translational regulation features to discover novel plant natural product biosynthetic pathways.
Identifiants
pubmed: 37549372
doi: 10.1002/anie.202307995
pmc: PMC10530425
mid: NIHMS1924117
doi:
Substances chimiques
mitragynine
EP479K822J
Secologanin Tryptamine Alkaloids
0
Antineoplastic Agents
0
Biological Products
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202307995Subventions
Organisme : NIDCD NIH HHS
ID : R21 DC019206
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM138826
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023 Wiley-VCH GmbH.
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