Search for novel metabolites in fungal endophytes: study of Phomopsis sp. and Colletotrichum sp. co-cultivation and Botryosphaeria mamane epigenetic modification

Fungal endophytes are fungi that grow within plant tissues without causing immediate signs of disease. They are gaining increased attention for their ability to produce natural products with diverse structure and pharmacological activity [1]. Under conventional cultures conditions some endophytes show loss of activity in producing secondary metabolites (SM) due to inactivation of metabolite gene clusters [2]. Several strategies have been applied to activate these silent gene clusters including epigenetic modifications and co-cultivation. The signal come to the cell will modify the silence gene and lead to an enhanced production and/or to an accumulation of different compounds that are not detected in axenic cultures [3].

The purpose of this study was to find new SM and analyze gene clusters activation through co-cultivation and through the addition of molecular and epigenetic modifier such as suberoylanilide hydroxamic acid or valproic acid into the culture medium. Our research group isolated 409 Ascomycetes strains from 21 medicinal plants from South America [4]. Among them, we chose Phomopsis sp. and Colletotrichum sp on the basis of ecological data as model for co-cultivation and Botrysosphaeria mamane for the epigenetic modification studies. First results obtained highlighted that the fungal co-cultivation can induce de novo synthesis of secondary metabolites (Barakat et al., data not published). In order to understand the mechanisms underlying these modifications, we focused on B. mamane, known to produce SM such as mellein, primin, botryomaman, and 4,5-dihydroxy-2-hexenoic acid[5]. This strain is being under investigation in our group for producing anti-leishmania SM. It exhibited good activity against Leishmania infantum with IC₅₀= 17. 04 µg/ml. Investigations are currently in process to apply epigenetic modifier in order to induce SM production in this strain and analyze its metabolomics and pharmacological activity modifications against L. infantum through immunomodulatory approaches.

Keywords: Fungal endophytes, co-cultivation, epigenetic, new metabolite production.

References:

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