Intein-mediated temperature control for complete biosynthesis of sanguinarine and its halogenated derivatives in yeast.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 Jun 2024
19 Jun 2024
Historique:
received:
01
01
2024
accepted:
10
06
2024
medline:
20
6
2024
pubmed:
20
6
2024
entrez:
19
6
2024
Statut:
epublish
Résumé
While sanguinarine has gained recognition for antimicrobial and antineoplastic activities, its complex conjugated structure and low abundance in plants impede broad applications. Here, we demonstrate the complete biosynthesis of sanguinarine and halogenated derivatives using highly engineered yeast strains. To overcome sanguinarine cytotoxicity, we establish a splicing intein-mediated temperature-responsive gene expression system (SIMTeGES), a simple strategy that decouples cell growth from product synthesis without sacrificing protein activity. To debottleneck sanguinarine biosynthesis, we identify two reticuline oxidases and facilitated functional expression of flavoproteins and cytochrome P450 enzymes via protein molecular engineering. After comprehensive metabolic engineering, we report the production of sanguinarine at a titer of 448.64 mg L
Identifiants
pubmed: 38898098
doi: 10.1038/s41467-024-49554-w
pii: 10.1038/s41467-024-49554-w
doi:
Substances chimiques
sanguinarine
AV9VK043SS
Isoquinolines
0
Benzophenanthridines
0
Cytochrome P-450 Enzyme System
9035-51-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5238Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 22278361, 32200052, and 32300053
Organisme : China Postdoctoral Science Foundation
ID : 2023M733096
Informations de copyright
© 2024. The Author(s).
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