Withanomics of Ashwagandha: The Specialized Metabolic Biology of an Ayurvedic Herb

Ashwagandha (Withania somnifera, Solanaceae) is one of the most significant medicinal plants of Ayurveda and is found in about 200 formulations of pharmaceutical/nutraceutical significance. It produces several characteristic bioactive secondary metabolites like withanolides, withanamides, calystegines, tropanes- each group covering a large number of individual phytochemicals. This metabolic diversity could be responsible for an assortment of therapeutic and nutraceutical traits generally attributed to the herb. Qualitative and quantitative variations in their biogeneration may originate from plant genotypic diversity or may vary with ontogeny, environment, seasonal/climatic regimes. Therefore, development of discrete chemotype diversity and clear delineation of the range of other variations are important for such botanicals in order to obtain more consistent medicinal/health benefits from them. Therefore, we have investigated metabolite diversity dynamics and specialized metabolic pathways of W. somnifera through conventional biochemical as well as 'omic' approaches (collectively named here as 'withanomics') leading to improved understanding such as (i) DOX pathway of isoprenogenesis contributes substantially to withanogenesis, (ii) roots and shoots possess independent metabolic pathways of de novo biosynthesis of withanolides, (iii) operation of a novel withanolidal cross-talk between shoot and roots (iv) discovery of several novel chemotypes and enzymes/genes of its specialized metabolism, (v) tissue-specific expression of tropine and pseudotropine forming reductases, (vi) predominatly tissue-restricted and ontogeny-specific expression of tryptophan decarboxylase, the committed step for withanamide biosynthesis, (vii) specific molecular pharmacology of chemotypes and withanolides. These observations are necessary in order to develop a Withania metabolic model/map and attempt transgenic or synthetic biology aided production of targeted phytochemical(s). Acknowledgements: New Millennium Indian Technology Leadership Initiative (CSIR).