Overexpression of the global regulator FnVeA upregulates antitumor substances in endophytic Fusarium nematophilum.

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Date: Aug. 2022
From: Canadian Journal of Microbiology(Vol. 68, Issue 8)
Publisher: NRC Research Press
Document Type: Report
Length: 6,981 words
Lexile Measure: 1470L

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Abstract :

The special niche of endophytic fungi promotes their potential to produce antitumor compounds with novel structure and significant bioactivity for screening of new antitumor drugs. In our previous studies, we isolated a Fusarium strain from the roots of the medicinal plant Nothapodytes pittosporoides and identified it as Fusarium nematophilum. We found that the crude extract of F. nematophilum had significant antitumor activity on A549 cancer cells, and overexpressing the global regulatory factor FnVeA (the VeA gene of the fungus F. nematophilum) resulted in a significant increase in the antitumor activity, which was approximately fivefold higher than wild strain for relative inhibition rate. In [FnVeA.sup.OE], the accumulation of indole, alkene, alkaloid, steroid, and flavonoid metabolites with potential antitumor activity was significantly upregulated compared with wild type via metabolomic analysis. Moreover, the transcriptome analysis showed that 134 differential genes were considered to be closely related to the biosynthesis of antitumor substances, of which 59 differential genes were considered as candidate key genes, and related to tryptophan dimethylallyltransferase, cytochrome P450 monooxygenase, polyketide synthases, and transcription factors. Taken together, we suggest that FnVeA may regulate the biosynthesis of antitumor substances by mediating the expression of genes related to secondary metabolic pathways in F. nematophilum. Key words: endophytic Fusarium nematophilum, fungal metabolites, global regulator VeA, antitumor, metabolome, transcriptome La niche speciale qu'occupent les champignons endophytes favorise leur potentiel de production de composes antitumoraux comportant une structure nouvelle et une bioactivite significative, a des fins de criblage de nouveaux medicaments antitumoraux. Lors d'etudes precedentes, les auteurs ont isole une souche de Fusarium a partir des racines de la plante medicinale Nothapodytes pittosporoides et l'ont identifiee comme etant Fusarium nematophilum. Ils ont constate que l'extrait brut de F. nematophilum possedait une activite antitumorale significative envers les cellules cancereuses A549, et que la surexpression du facteur de regulation global FnVeA (le gene VeA du champignon F. nematophilum) entrainait une augmentation significative de l'activite antitumorale, qui etait environ 5 fois superieure a celle de la souche sauvage en ce qui concerne le taux d'inhibition relatif. Chez la souche FnVeA OE, l'accumulation de metabolites, soit des indoles, alcenes, alcaloides, de steroides et flavonoides presentant une activite antitumorale potentielle etait significativement regulee a la hausse par rapport a la souche sauvage selon une analyse metabolomique. En outre, l'analyse du transcriptome a montre que 134 genes differentiellement exprimes etaient consideres comme etroitement lies a la biosynthese de substances antitumorales, dont 59 genes consideres comme des genes cles candidats, et lies a la tryptophane dimethylallyltransferase, a la monooxygenase du cytochrome P450, aux polyketides synthases et a des facteurs de transcription. Dans l'ensemble, les auteurs suggerent que FnVeA peut reguler la biosynthese de substances antitumorales en mediant l'expression de genes lies aux voies metaboliques secondaires chez F. nematophilum. [Traduit par la Redaction] Mots-cles : Fusarium nematophilum endophyte, metabolites fongiques, regulateur global VeA, antitumoral, metabolome, transcriptome

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Gale Document Number: GALE|A715418815