Enhancing Withanolide Production in the Withania Species: Advances in In Vitro Culture and Synthetic Biology Approaches

Abstract

Withanolides are naturally occurring steroidal lactones found in certain species of the Withania genus, especially Withania somnifera (commonly known as Ashwagandha). These compounds have gained considerable attention due to their wide range of therapeutic properties and potential applications in modern medicine. To meet the rapidly growing demand for withanolides, innovative approaches such as in vitro culture techniques and synthetic biology offer promising solutions. In recent years, synthetic biology has enabled the production of engineered withanolides using heterologous systems, such as yeast and bacteria. Additionally, in vitro methods like cell suspension culture and hairy root culture have been employed to enhance withanolide production. Nevertheless, one of the primary obstacles to increasing the production of withanolides using these techniques has been the intricacy of the biosynthetic pathways for withanolides. The present article examines new developments in withanolide production through in vitro culture. A comprehensive summary of viable traditional methods for producing withanolide is also provided. The development of withanolide production in heterologous systems is examined and emphasized. The use of machine learning as a potent tool to model and improve the bioprocesses involved in the generation of withanolide is then discussed. In addition, the control and modification of the withanolide biosynthesis pathway by metabolic engineering mediated by CRISPR are discussed.