A new study has uncovered key enzymes involved in the production of Taxol, a chemotherapy drug derived from yew trees. This breakthrough could significantly enhance the efficiency and cost-effectiveness of producing the drug using industrial microbes.
Taxol, also known as paclitaxel, is used to treat various cancers but has been challenging to produce due to its complex structure. Traditionally extracted from slow-growing yew trees, the demand for Taxol far exceeds supply. Scientists have long sought to identify the enzymes responsible for its biosynthesis to enable microbial production.
Conor McClune, a postdoctoral scholar in chemical engineering, stated, “We really need enzymes to build this molecule,” highlighting their efficiency and cleanliness in chemical reactions.
McClune and his team at Stanford University developed a novel method to analyze plant genes. Their research identified several crucial enzymes for creating Taxol, bringing them closer to producing it efficiently through industrial microbes. Elizabeth Sattely, an associate professor of chemical engineering and senior author of the study published in Nature on June 11, remarked, “Being able to use a bioproduction strategy to manufacture a molecule like Taxol is a really exciting prospect.”
The team faced challenges with the massive genome of yew trees compared to simpler organisms like E. coli. By stressing yew tree samples with hormones and microbes, they induced defensive compound production and isolated about 10,000 nuclei for sequencing. This approach allowed them to identify eight new genes critical for making Taxol.
One enzyme called FoTO1 was particularly significant in streamlining the reaction process. The tobacco plants used in experiments produced baccatin III at higher concentrations than found in yew trees. McClune noted that with further refinement, they might no longer need yews for baccatin production.
Additionally, scientists at the University of Copenhagen recently identified two final enzyme pieces needed for completing Taxol synthesis from baccatin III. With these discoveries combined, researchers now possess what may be considered the complete set of genes necessary for synthesizing Taxol from scratch.
The next step involves verifying whether these final two enzymes work with other genes in tobacco plants before potentially inserting them into yeast strains engineered as efficient chemical factories.
This new gene analysis method could lead to more discoveries in plant chemistry beyond just yews; common crops are also under investigation by McClune’s team due to their rich enzymatic activities.
Sattely is affiliated with Howard Hughes Medical Institute and Stanford Bio-X among other institutions while Fordyce contributes through SPARK at Stanford alongside others such as PhD student Jack Chun-Ting Liu who co-leads this research effort supported financially by organizations including NIH & Damon Runyon Cancer Research Foundation among others mentioned earlier too!
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