A Decade of Molecular Understanding of Withanolide Biosynthesis and In vitro Studies in Withania somnifera (L.) Dunal: Prospects and Perspectives for Pathway Engineering

Abstract

Withania somnifera, a multipurpose medicinal plant is a rich reservoir of pharmaceutically active triterpenoids that are steroidal lactones known as withanolides. Though the plant has been well-characterized in terms of phytochemical profiles as well as pharmaceutical activities, limited attempts have been made to decipher the biosynthetic route and identification of key regulatory genes involved in withanolide biosynthesis. This scenario limits biotechnological interventions for enhanced production of bioactive compounds. Nevertheless, recent emergent trends vis-à-vis, the exploration of genomic, transcriptomic, proteomic, metabolomics, and in vitro studies have opened new vistas regarding pathway engineering of withanolide production. During recent years, various strategic pathway genes have been characterized with significant amount of regulatory studies which allude toward development of molecular circuitries for production of key intermediates or end products in heterologous hosts. Another pivotal aspect covering redirection of metabolic flux for channelizing the precursor pool toward enhanced withanolide production has also been attained by deciphering decisive branch point(s) as robust targets for pathway modulation. With these perspectives, the current review provides a detailed overview of various studies undertaken by the authors and collated literature related to molecular and in vitro approaches employed in W. somnifera for understanding various molecular network interactions in entirety.

Ascertaining the Paradigm of Secondary Metabolism Enhancement through Gene Level Modification in Therapeutic Plants

“…31 Using this method the production of pharmaceutically important secondary metabolites in plants, for instance; Papaver somniferum, P. ginseng, A. annua and W. somnifera. 32,33 Using this method researchers have developed a process for production of non-narcotic alkaloid, reticuline in opium poppy, which is more potent than morphine. Here gene encoding Codeinone Reductase (COR), a key enzyme of morphine biosynthetic pathway was silenced.…”

Withania somnifera: Advances and Implementation of Molecular and Tissue Culture Techniques to Enhance Its Application

“…Till date, complete information of whole withanolide biosynthesis pathway is not available. However, combination of several studies provide an overview of pathway illustrating several enzymatic steps (Mirjalili et al, 2009 ; Senthil et al, 2010 ; Chaurasiya et al, 2012 ; Gupta et al, 2013a , b , 2015 ; Dhar et al, 2015 ). Enzymatic steps of MVA and MEP pathways has been prescribed through the first transcriptome analysis of the plant (Senthil et al, 2010 ), which keeps improving with advancement in techniques (Gupta et al, 2013b , 2015 ; Senthil et al, 2015 ).…”

“…To understand the interactions of various molecular network in entirety, Dhar et al ( 2015 ) and Singh et al ( 2015b ) summarized the available information of some in vitro studies with respect to regulation of pathway genes required for withanolide accumulation.…”

Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin

“…Solanacea), also known as Ashwagandha, it is found to be loaded with numerous medicinal properties and useful in counteracting various illness like dehydration, muscle tension, memory loss and also restoring general health and vitality. This plant is known to be found globally, with more occurrences in xeric and drier regions of tropical and subtropical areas [2,3]. We have selected four derivatives of this plant, which are withanolide A (C 28 activities like chemopreventive, anti-inflammatory, anti-arthritic, and angiogenesis activity [4], and they are being used as a rasayana to promote immunity,health and longevity which acts as a adaptogen and immunomodulator.…”