page_title: Withaferin A
section_title: Biosynthesis
hierarchical_section_title: Withaferin A / Biosynthesis
caption_attribution_description: English: Proposed mechanism for 6-membered lactone ring formation in the biosynthesis of Withaferin A.
context_page_description: Withaferin A is a steroidal lactone, derived from Acnistus arborescens, Withania somnifera and other members of family Solanaceae. It has been traditionally used in ayurvedic medicine. It is the first member of the withanolide class of ergostane type product to be discovered. This natural product has wide range of pharmacological activities including cardioprotective, anti-inflammatory, immuno-modulatory, anti-angiogenesis, anti-metastasis and anti-carcinogenic properties.
context_section_description: In the withania somnifera plant, the withanolide, Withaferin A, is present in the leaves. Withanolides are terpenoids, which are synthesized in plants using isoprenoids as precursors. Isoprenoids can be synthesized through mevalonate (MVA) or 1-deoxy-D-xylulose 5-phosphate (DOXP) pathways. Isoprenogenesis significantly governs withanolide synthesis.
  Isoprenoids form squalene, which then goes through a variety of intermediate steps to form 24-methylenecholesterol - the sterol precursor of the withanolides.
  The biosynthesis of Withaferin A utilizes a variety of enzymes such as squalene epoxidase (SQE), cycloartenol synthase (CAS), sterol methyl transferase (SMT), obtusifoliol-14 –demethylase (ODM). Upregulation of expression of these key enzymes could potentially enhance Withaferin A content in the leaves.
  To produce Withaferin A from 24-methylene cholesterol, the molecule undergoes several functional changes including formation of a ketone, epoxide, 2 hydroxyl groups, and lactone ring.
caption: Lactone ring formation in Withaferin A biosynthesis.
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