Discovery and Activation of the Cryptic Cluster from Aspergillus sp. CPCC 400735 for Asperphenalenone Biosynthesis.
ACS Chem Biol
; 17(6): 1524-1533, 2022 06 17.
Article
em En
| MEDLINE
| ID: mdl-35616995
ABSTRACT
Postgenomic analysis manifested that filamentous fungi contain numerous natural product biosynthetic gene clusters in their genome, yet most clusters remain cryptic or down-regulated. Herein, we report the successful manipulation of strain Aspergillus sp. CPCC 400735 that enables its genetic engineering via targeted overexpression of pathway-specific transcriptional regulator AspE. The down-regulated metabolic pathway encoded by the biosynthetic gene cluster asp was successfully up-activated. Analyses of mutant Ai-OEaspE extracts led to isolation and characterization of 13 asperphenalenone derivatives, of which 11 of them are new compounds. All of the asperphenalenones exhibited conspicuous anti-influenza A virus effects with IC50 values of 0.45-2.22 µM. Additionally, their identification provided insight into biosynthesis of asperphenalenones and might benefit studies of downstream combinatorial biosynthesis. Our study further demonstrates the effective application of targeted overexpressing pathway-specific activator and novel metabolite discovery in microorganisms. These will accelerate the exploitation of the untapped resources and biosynthetic capability in filamentous fungi.
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Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Vias Biossintéticas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article