Researchers at the Indian Institute of Technology Madras (IIT Madras) and IIT Mandi have metabolically engineered the plant cells of Nothapodytes nimmoniana, a flowering plant native to the Indian subcontinent, to increase the production of Camptothecin, a drug used to treat cancer.
Camptothecin is the lead molecule in anti-cancer high-value chemotherapy drugs like Topotecan and Irinotecan. However, nearly 1,000 tons of plant material is required to extract a ton of Camptothecin. Moreover, the N. nimmoniana plant declined by 20 per cent in the last decade alone.
Due to climate change and overharvesting to meet the market demand, camptothecin plant sources were red-listed by the International Union for Conservation of Nature (IUCN). To address the issue, researchers at IIT Madras’s Plant Cell Technology Lab have developed a genome-scale metabolic model for N. Nimmoniana plant cells using computational tools, a news release by the institute stated.
The research was led by Sarayu Murali, a PhD student at IIT Madras. It was funded by the Science and Engineering Board (SERB) and the Department of Science and Technology (DST), Government of India.
Explaining the technical aspects of this research, Murali said, "The metabolic model was reconstructed and curated using in-house experimental data. Computational tools were then used to identify and rank suitable enzyme targets for overexpression and downregulation to maximize camptothecin production in N. nimmoniana plant cells.”
She further explained, “We experimentally validated the overexpression of an enzyme predicted by the model, which led to the development of a 5-fold high camptothecin-yielding cell line of N. nimmoniana in comparison to the untransformed plant cell line."
Cancer is a major public health problem worldwide and is the second leading cause of death in the U.S. As per the World Health Organization (WHO), cancer accounted for nearly 10 million deaths, or nearly one in six deaths globally in 2020. In India, the number of cancer cases are expected to rise to 1.7 million by 2025, according to the Indian Council of Medical Research – National Cancer Registry Program (ICMR-NCRP 2020).
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