Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones.
Amyloid beta-Peptides
/ metabolism
Animals
Anti-HIV Agents
/ pharmacology
Aspergillus
/ chemistry
Biosynthetic Pathways
/ drug effects
Cell Proliferation
/ drug effects
Diterpenes
/ chemistry
Drosophila
/ drug effects
Fungi
/ chemistry
Genome, Fungal
HIV-1
/ drug effects
Humans
MCF-7 Cells
Naphthalenes
/ chemistry
Neoplastic Stem Cells
/ drug effects
Protein Aggregates
Pyrones
/ chemistry
Spheroids, Cellular
/ drug effects
Stereoisomerism
Synthetic Biology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 04 2020
14 04 2020
Historique:
received:
18
10
2019
accepted:
19
03
2020
entrez:
15
4
2020
pubmed:
15
4
2020
medline:
22
7
2020
Statut:
epublish
Résumé
A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product with novel structures and biological activities through total biosynthesis and combinatorial biosynthesis. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs). Genome mining reveals putative DDP biosynthetic gene clusters distributed in five fungal genera. In addition, we design extended DDP pathways by combinatorial biosynthesis. In total, ten DDP pathways, including five native pathways, four extended pathways and one shunt pathway, are heterologously reconstituted in a genetically tractable heterologous host, Aspergillus oryzae, resulting in the production of 22 DDPs, including 15 new analogues. We also demonstrate the advantage of expanding the diversity of DDPs to probe various bioactive molecules through a wide range of biological evaluations.
Identifiants
pubmed: 32286350
doi: 10.1038/s41467-020-15664-4
pii: 10.1038/s41467-020-15664-4
pmc: PMC7156458
doi:
Substances chimiques
Amyloid beta-Peptides
0
Anti-HIV Agents
0
Diterpenes
0
Naphthalenes
0
Protein Aggregates
0
Pyrones
0
decalin
88451Q4XYF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1830Références
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