IITs' Innovation: Amplifying Camptothecin Production for Cancer Treatments

Camptothecin (CPT) is an important anti-cancer drug lead molecule for high-value drugs like Topotecan and Irinotecan. The researchers from the Plant Cell Technology Lab of IIT Madras have developed a genome-scale metabolic model for N nimmoniana plant cells using computational tools. 

Researchers from Indian Institute of Technology Madras (IIT Madras) and IIT Mandi have achieved a significant breakthrough by metabolically engineering the plant cells of Nothapodytes nimmoniana to enhance the production of Camptothecin, a crucial anti-cancer compound.

Camptothecin, the third most in-demand alkaloid globally, is primarily extracted from Nothapodytes nimmoniana, an endangered plant native to India. Due to rampant overharvesting, major plant sources of Camptothecin are now red-listed by the International Union for Conservation of Nature (IUCN), with the N. nimmoniana population declining by over 20% in the past decade alone.

Led by Sarayu Murali, a PhD student at IIT Madras, and co-guided by Dr. Maziya Ibrahim, Professors Karthik Raman, and Smita Srivastava from the Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, IIT Madras, along with Dr. Shyam Kumar Masakapalli from IIT Mandi's School of Biosciences and Bioengineering, and Shagun Saini from IIT Mandi's Metabolic Systems Biology Lab, the team developed a genome-scale metabolic model for N. nimmoniana plant cells using advanced computational tools.

Their research, supported by the Science and Engineering Board (SERB) and the Department of Science and Technology (DST) of the Government of India, was recently published in the peer-reviewed Journal Frontiers of Plant Science. This pioneering work aims to address the escalating market demand for Camptothecin sustainably while conserving natural resources.

Prof. Smita Srivastava, the Principal Investigator of the project, emphasized, "Integration of metabolic engineering with bioprocess engineering principles can ensure enhanced and sustainable production of Camptothecin, meeting market demand efficiently and conserving natural resources."

Highlighting the broader impact of their findings, Prof. Karthik Raman, co-investigator of the study, noted, "This platform technology can be adapted for enhancing production of various other high-value phytochemicals, reducing our reliance on natural sources."

Camptothecin is a critical compound used in the development of anti-cancer drugs such as Topotecan and Irinotecan, making advancements in its production crucial in the face of rising cancer incidences worldwide. According to the World Health Organization (WHO), cancer accounted for nearly 10 million deaths globally in 2020, with India projected to see a rise in cases to 15.7 lakh by 2025, according to the Indian Council of Medical Research-National Cancer Registry Programme (ICMR-NCRP 2020).

Murali detailed the technical aspects of their approach, stating, "We reconstructed and curated the metabolic model using experimental data, employing computational tools to identify enzyme targets for optimizing Camptothecin production in N. nimmoniana plant cells. Experimental validation led to the development of a cell line yielding five times more Camptothecin compared to the untransformed plant cells."

Dr. Shyam Kumar Masakapalli highlighted the scientific strategies employed, stating, "Our work lays the foundation for engineering plant cell bio-factories to sustainably manufacture high-value phytochemicals like Camptothecin, addressing critical needs in cancer treatment."

This research not only represents a significant advancement in biotechnology and metabolic engineering but also underscores the importance of sustainable practices in pharmaceutical development, ensuring continued access to life-saving treatments while preserving biodiversity.