Indian scientists have turned plant cells into tiny biofactories that produce a key raw material for several anti-cancer medicines, an alternative source to obtain a compound hitherto extracted from endangered plant species.

The researchers who combined tricks from plant genetic engineering with computer simulations have also increased five-fold the per gram production yield of the compound called camptothecin that has been traditionally harvested from rare plants.

Camptothecin is an organic compound found in plants such as Nothapodytes nimmoniana — a small tree native to India’s Western ghats and commonly called “stinking tree” or “fetid holly”. The compound is used in the synthesis of four chemotherapy medicines used in the treatment of breast, colon, gastric, lung, and ovarian cancers.

But the tree grows slowly, taking an average of seven years to mature and yield camptothecin in commercially attractive amounts. A growing market demand for the compound has meant excessive exploitation, leading to sharp depletions of the species population.

“Uprooting this already-endangered tree year after year is not a sustainable way to get camptothecin,” said Smita Srivastava, a professor who specialises in biochemical engineering at the Indian Institute of Technology Madras, who led the research.

Scientists in China had in 2012 announced a process for the full chemical synthesis of camptothecin with 99.9 per cent purity from scratch, but the process is cumbersome and impractical and the demand for the trees has persisted unabated.

Srivastava and her colleagues decided to explore the use of plant tissue cell cultures as a source of the compound. Tissue culture is a decades-old technology in which plant cells are grown in the lab and fed on a broth of nutrients.

Camptothecin is a natural product made by the fetid holly tree as a defence against predators — insects or mammals that might come to feed on the tree. The IIT Madras team collaborating with scientists at IIT Mandi cultured camptothecin-producing cells from the tree in the lab.

The researchers then used computer simulations to tweak multiple biological pathways in the cells to find a way to maximise their yield of camptothecin. “Imagine a complex network of roads and you want to direct certain traffic to a certain destination — where the goal is to maximise camptothecin yield,” said Karthik Raman, professor of biotechnology and member of the Robert Bosch Centre for Data Science and Artificial Intelligence at IIT, Madras.

Their computer analysis pointed to 23 possible pathways through which the cells could overproduce camptothecin. The researchers selected one that promised the maximum yield and manipulated genes within the cells to implement those pathways in the lab.

“The genetic engineering in the cells is equivalent to widening the roads for the traffic — to achieve higher camptothecin yields,” Raman said. The scientists have published their findings in the peer-reviewed journal Frontiers in Plant Science.

The genetically engineered cells produced five micrograms of camptothecin per gram cellular material, or five-fold higher than what is available from natural plant cells. Srivastava said the research results are encouraging enough for future efforts to scale the process upward for industrial-level production.