Kerala-born Parayil Kumaran Ajikumar and his colleagues at Massachusetts Institute of Technology and Tuffts University have come up with a novel method to produce a precursor to taxol using common bacteria.
The precursor molecule can subsequently be used to produce this popular but hugely expensive drug in bulk quantity, which ultimately would bring down manufacturing cost. For cancer patients, one dose of taxol costs about $10,000. Typically most patients receive only one dose.
In 1971, Maharashtrian scientist Mansukh C Wani and his American partner Monroe Wall discovered the blockbuster drug, which is extensively being used to treat lung, ovary, breast, head and neck cancer.
They isolated the drug from the bark of Pacific Yew tree, which remained the primary drug source till recently. Even in early 1990s, a mere 286 pounds of the life-saving drug was extracted from 1,000 tonnes of bark, which required cutting down of more than half a million mature Pacific Yew trees.
Later in the last decade, bio-engineers came up with another method to produce the drug. But production rate was inadequate to have an adequate supply of the drug to synthesise more potent variants of taxol. The procedure was cumbersome with low yield.
That is where Ajikumar and his colleagues’ intervention becomes valuable. Even more promising is the fact that their tiny cancer drug factory cannot only produce taxol but other drugs also.
“If you can make taxol a lot cheaper, that’s good, but what really gets people excited is the prospect of using our platform to discover other therapeutic compounds in an era of declining new pharmaceutical products,” said Gregory Stephanopoulos, a MIT chemical engineering professor who guided Ajikumar.
By mimicking nature, the engineered E-coli bacteria can produce 1,000 times more of these precursors than any other engineered microbes. The key was in tweaking the taxol-synthesis pathway in a manner to maximise the production of the precursor molecule, taxadiene.
The MIT team has applied for a patent and plans to start a company to commercialise the product. Researchers could experiment with using these bacteria to create other useful chemicals such as fragrances, flavours and cosmetics too, said Ajikumar, who did his PhD from MG University, Kerala. The new technique was reported in the journal Science on Friday.
Now that the researchers have achieved taxadiene synthesis, there are still another 15 to 20 steps to go before they can generate taxol. The scientists showed that they can perform the first of those steps.
The same approach could be applied to many important natural products. Complex “green” chemicals could be made more affordable if feed-stocks like taxadiene become commonly available, said Tianang Liu and Chaitan Khosla, both chemical engineers at Stanford University.