IIT Madras and IIT Mandi researchers metabolically engineer plant cells
IIT Madras and IIT Mandi researchers have metabolically engineered the plant cells of Nothapodytes nimmoniana to increase the production of Camptothecin, which is used to treat cancer.
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.
Research paper
In a Research Paper published in 2021, IIT Madras researchers identified a microbe as a sustainable and high-yielding alternative source for the plant-derived anti-cancer drug Camptothecin.
Nearly 1,000 tons of plant material is required to extract just one ton of Camptothecin, say sources from IIT Madras.
Due to extensive overharvesting to meet the market demand its major plant sources are now red-listed as per IUCN.
The N. nimmoniana population has seen more than a 20 per cent decline in the last decade alone, say sources from IIT Madras.
Metabolic Engineering
In the current research, metabolic engineering of the plant cells using a genome-scale metabolic model was led by Ms. Sarayu Murali, PhD student, IIT Madras, Dr. Maziya Ibrahim, Computational Systems Biology Lab, IIT Madras, Prof. Karthik Raman and Prof. Smita Srivastava, Department of Biotechnology, IIT Madras, along with Dr. Shyam K. Masakapalli and Ms. Shagun Saini from Metabolic Systems Biology Lab, IIT Mandi.
Research
The research was funded by the Science and Engineering Board (SERB) and the Department of Science and Technology (DST), Government of India.
This study was recently published in the peer-reviewed Journal Frontiers of Plant Science (https://doi.org/10.3389/fpls.2023.1207218).
Prof Smita said integration of metabolic engineering with bioprocess engineering principles can ensure enhanced and sustainable production of Camptothecin, to continuously meet its increasing market demand in minimum time and cost in addition to natural resource conservation.
Platform
Further, the Co-investigator of the study Prof. Karthik Raman, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, IIT Madras, added this platform technology for model-based rational metabolic engineering of plant cells can be adapted to enhance the production of many other high-value phytochemicals as well.
This study can pave the way for effective and efficient commercial production of camptothecin and other medicinally important monoterpene indole alkaloids, with reduced dependence on nature, said Prof Karthik Raman of IIT Madras.
CPT
Camptothecin (CPT) is an important anti-cancer drug lead molecule for high-value drugs like Topotecan and Irinotecan, say sources from IIT Madras.
It is a potent topoisomerase I inhibitor extracted mainly from – Camptotheca acuminata (native to Eastern Asia) and Nothapodytes nimmoniana (native to India).
However, the conjunction of climate change and extensive deforestation undertaken for CPT extraction has pushed these plants into the endangered species category, say sources from IIT Madras.
It is satisfying to collaborate with the Plant Cell Technology Lab at IIT Madras, which has developed a potential platform for five-fold increased synthesis of camptothecin, a much-needed anti-cancer phytochemical, he said.
Technical aspects
Elaborating on the technical aspects of this research, First Author of the Research Paper Ms. Sarayu Murali, PhD student, IIT Madras, 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.
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, he said.
In India, the number of cases is expected to rise to 15.7 lakh by 2025 according to the Indian Council of Medical Research-National Cancer Registry Programme (ICMR-NCRP 2020).
With increasing cancer incidences each day, the demand for enhanced production of anti-cancer drugs has been a compelling need of the hour.
S Vishnu Sharmaa is with collegechalo.com in the news team where he writes articles related to the education sector in India. Journalism has always been a passion for him. He has over 20 years of enriching experience with various media organizations like Eenadu, Webdunia, News Today, Infodea. He also has a strong interest in writing stories related to Indian defense and Indian Railways.