AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria.

Autor: Feng C; College of Pharmacy, Guizhou University, Guiyang, People's Republic of China.; Southwest Biomedical Resources of the Ministry of Education, Guizhou University, Guiyang, People's Republic of China., Zheng W; Southwest Biomedical Resources of the Ministry of Education, Guizhou University, Guiyang, People's Republic of China., Han L; Southwest Biomedical Resources of the Ministry of Education, Guizhou University, Guiyang, People's Republic of China., Wang JK; Southwest Biomedical Resources of the Ministry of Education, Guizhou University, Guiyang, People's Republic of China., Zha XP; Southwest Biomedical Resources of the Ministry of Education, Guizhou University, Guiyang, People's Republic of China., Xiao Q; Southwest Biomedical Resources of the Ministry of Education, Guizhou University, Guiyang, People's Republic of China., He ZJ; College of Pharmacy, Guizhou University, Guiyang, People's Republic of China.; Southwest Biomedical Resources of the Ministry of Education, Guizhou University, Guiyang, People's Republic of China., Kang JC; College of Pharmacy, Guizhou University, Guiyang, People's Republic of China.; Southwest Biomedical Resources of the Ministry of Education, Guizhou University, Guiyang, People's Republic of China.
Jazyk: angličtina
Zdroj: Journal of basic microbiology [J Basic Microbiol] 2024 Jan; Vol. 64 (1), pp. 68-80. Date of Electronic Publication: 2023 Sep 17.
DOI: 10.1002/jobm.202300319
Abstrakt: Endophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeA OE26 , which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeA OE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD-binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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