Global regulatory factor AaLaeA upregulates the production of antitumor substances in the endophytic fungus Alternaria alstroemeria.
J Basic Microbiol
; 62(11): 1402-1414, 2022 Nov.
Article
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| MEDLINE
| ID: mdl-36041052
ABSTRACT
The global regulatory factor LaeA has been shown to be involved in the biosynthesis of secondary metabolites in various fungi. In a previous work, we isolated an endophytic fungus from Artemisia annua, and its extract had a significant inhibitory effect on the A549 cancer cell line. Phylogenetic analysis further identified the strain as Alternaria alstroemeria. Overexpression of AalaeA gene resulted in significantly increased antitumor activity of this strain's extract. The 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay results showed that the inhibition rate of the AalaeAOE29 mutant extract on A549 cancer cells was significantly higher than that of the WT extract, as the IC50 decreased from 195.0 to 107.4 µg/ml, and the total apoptosis rate was enhanced. Overexpression of the AalaeA gene significantly increased the contents of myricetin, geraniol, ergosterol, and 18 other antitumor compounds as determined by metabolomic analysis. Transcriptomic analysis revealed significant changes in 95 genes in the mutant strain, including polyketide synthases, nonribosomal peptide synthases, cytochrome P450s, glycosyltransferases, acetyl-CoA acetyltransferases, and others. These results suggested that AaLaeA mediated the antitumor activity of the metabolites in A. alstroemeria by regulating multiple metabolic pathways.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Alstroemeria
/
Alternaria
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Basic Microbiol
Asunto de la revista:
MICROBIOLOGIA
Año:
2022
Tipo del documento:
Article