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Tissue specific biosynthesis of secondary metabolites is a distinguished feature of medicinal plants.  Withania somnifera , source of pharmaceutically important withanolides biosynthesizes withaferin-A in leaves and withanolide-A in roots. To increase the  in planta  withanolides production, a sustainable approach needs to be explored. Here, we isolated endophytes from different parts of  W. somnifera  plants and their promising role in  in planta  withanolide biosynthesis was established in both  in-vivo  grown as well in  in-vitro  raised composite  W. somnifera  plants. Overall, the fungal endophytes improved photosynthesis, plant growth and biomass, and the root-associated bacterial endophytes enhanced the withanolide content in both  in-vivo  and  in-vitro  grown plants by modulating the expression of withanolide biosynthesis genes in leaves and roots. Surprisingly, a few indole-3-acetic acid (IAA)-producing and nitrogen-fixing root-associated endophytes could induce the biosynthesis of withaferin-A in roots by inducing  in planta  IAA-production and upregulating the expression of withanolide biosynthesis genes especially MEP-pathway genes ( DXS  and  DXR ) in roots as well. Results indicate the role of endophytes in modulating the synthesis and site of withanolides production and the selected endophytes can be used for enhancing the  in planta  withanolide production and enriching roots with pharmaceutically important withaferin-A which is generally absent in roots.

Endophytes of Withania somnifera modulate in planta content and the site of withanolide biosynthesis