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<p><i>Centella asiatica</i> is a medicinal plant that is effective in medicine due to the presence of bioactive triterpenoid saponins known as centellosides, which comprise of asiaticoside, madecassoside and others. Although centellosides also have significance in medicine, they are not naturally accumulated in large amounts and their quantity differs greatly between tissues, developmental stages and environmental conditions. This review integrates the existing developments in microbiological, molecular, biochemical, and biotechnological schemes, that can be used to enhance centelloside production through the regulation of metabolic and regulatory pathways. Particular emphasis is placed on the coordinated activation of the HMGR-SQS-β-AS-CYP716-UGT route in a co-ordinated manner. This route regulates the steps of producing precursors, β-amyrin cyclization, oxidation, and glycosylation. Activation of transcription factors (MYC2, WRKY, MYB, AP2/ERF), initiation of Reactive oxygen species (ROS)-Ca<sup>2+</sup> signaling, and manipulation of information flow into triterpenoid biosynthesis have become a potent method of activation by means of methyl jasmonate (MeJA), coronatine, feeding on precursors, nanoparticles and light modulation. Additional microbial interactions with rhizobacteria, endophytes and arbuscular mycorrhizal fungi also increase the metabolite accumulation by altering root exudates, transporting nutrients and altering the expression of defense related genes. The current challenges and prospects of metabolic engineering include CRISPR-based editing, reconstruction, and overexpression of SQS1 and CYP716A83, which allow stable and high-yield production that is independent of field changes. Bioreactor systems (Plantform™, RITA<sup>®</sup>) and synthetic microbial consortia provide scalable platforms, while transcriptional, post-transcriptional, and epigenetic regulatory breakthroughs increase precise control. In this review, a biochemical-molecular framework for centelloside biosynthesis is developed to promote sustainable medicinal and commercial uses.</p> Graphical abstract <p></p>

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Microbial-Molecular Synergy for Enhancing Centelloside Biosynthesis in Centella asiatica Integrating Genetic Regulation and Sustainable Elicitation

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Shruti Singh,
  • Devendra Kumar Pandey,
  • Sudhir Kumar Upadhyay

摘要

Centella asiatica is a medicinal plant that is effective in medicine due to the presence of bioactive triterpenoid saponins known as centellosides, which comprise of asiaticoside, madecassoside and others. Although centellosides also have significance in medicine, they are not naturally accumulated in large amounts and their quantity differs greatly between tissues, developmental stages and environmental conditions. This review integrates the existing developments in microbiological, molecular, biochemical, and biotechnological schemes, that can be used to enhance centelloside production through the regulation of metabolic and regulatory pathways. Particular emphasis is placed on the coordinated activation of the HMGR-SQS-β-AS-CYP716-UGT route in a co-ordinated manner. This route regulates the steps of producing precursors, β-amyrin cyclization, oxidation, and glycosylation. Activation of transcription factors (MYC2, WRKY, MYB, AP2/ERF), initiation of Reactive oxygen species (ROS)-Ca2+ signaling, and manipulation of information flow into triterpenoid biosynthesis have become a potent method of activation by means of methyl jasmonate (MeJA), coronatine, feeding on precursors, nanoparticles and light modulation. Additional microbial interactions with rhizobacteria, endophytes and arbuscular mycorrhizal fungi also increase the metabolite accumulation by altering root exudates, transporting nutrients and altering the expression of defense related genes. The current challenges and prospects of metabolic engineering include CRISPR-based editing, reconstruction, and overexpression of SQS1 and CYP716A83, which allow stable and high-yield production that is independent of field changes. Bioreactor systems (Plantform™, RITA®) and synthetic microbial consortia provide scalable platforms, while transcriptional, post-transcriptional, and epigenetic regulatory breakthroughs increase precise control. In this review, a biochemical-molecular framework for centelloside biosynthesis is developed to promote sustainable medicinal and commercial uses.

Graphical abstract