Navigation Links
Researchers advance biosynthesis of potent anti-cancer drug Taxol
Date:9/30/2010

MEDFORD/SOMERVILLE, Mass.--Researchers from Tufts University School of Engineering and MIT have reported a new way to biosynthesize important precursors to the potent anti-cancer compound Taxol in an engineered strain of E. coli bacteria.

The findings are significant steps on the way to achieving cost-effective, large-scale production of Taxol and the effort to design new Taxol-like pharmaceuticals.

The work is reported in the October 1, 2010, issue of the journal Science.

Taxol (paclitaxel) and its structural analogs are among the most powerful and commercially successful anticancer drugs, used to treat Kaposi's sarcoma and breast, lung and ovarian tumors.

Taxol was originally derived from the bark of the Pacific yew tree. Its anti-cancer properties were discovered more than 40 years ago.

But Taxol's power comes with an environmental price: Early stage production methods required sacrificing two to four fully grown trees for each patient. Alternative means of production such as using needles rather than bark still rely on slow, laborious plant-based processes. This limits production of Taxol itself and development of new derivatives that might be even more effective.

"This was the basis for our efforts to redirect biosynthesis through a simple, process-friendly bacterium like E. coli," explains Tufts' Blaine Pfeifer, Ph.D., assistant professor of chemical and biological engineering and co-corresponding author on the paper. "We faced a tremendous challenge because of the engineering needed first to 'equip' the E. coli cell to support Taxol biosynthesis and the subsequent protein engineering required to allow the first two steps in the Taxol biosynthesis scheme to be active within this new host."

The complex metabolic sequence that produces Taxol involves at least 17 intermediate steps and is not fully understood. The team's goal was to optimize production of the first two Taxol intermediates, taxadiene and taxadien-5alpha-ol.

The researchers partitioned the taxadiene metabolic pathway into two modules: the intracellular supply of substrates, or precursors, that must be present within the E. coli cell before Taxol can be produced (the upstream pathway) and the biosynthetic steps needed to make the first two Taxol intermediates (the downstream pathway).

This modular approach allowed manipulation of the many variables in each pathway to achieve the right balance to optimize production of the two intermediates. It effectively "unlocked" unprecedented production levels of early-stage Taxol intermediates through E. coli.

The team reported producing more than 1 gram of taxadiene per liter of production culture a level that was 1,000 times greater than had previously been reported using E. coli as a host and 15,000 times more than the study's initial production levels prior to balancing the upstream and downstream modular pathways. For the first time, the second Taxol precursor, taxadiene-5alpha-ol, was produced from E. coli.

The researchers caution that significant work is still needed in order to complete the synthesis of a Taxol precursor suitable for commercial production and potentially replace the current plant-based production process with a more efficient operation based upon microbial biosynthesis. Such an approach could also be applied to production of chemicals and fuels microbially derived from renewable resources.

"Though this is only a first step, it is a very promising development and certainly supports this approach and its potential," said Pfeifer.


'/>"/>

Contact: Kim Thurler
kim.thurler@tufts.edu
617-627-3175
Tufts University
Source:Eurekalert

Related medicine news :

1. Researchers map all the fragile sites of the yeast Saccharomyces cerevisiaes genome
2. UH Case Medical Center researchers publish promising findings for advanced cervical cancer
3. Researchers discover new way to kill pediatric brain tumors
4. Researchers Who Discovered First Genes for Stuttering will Present Findings to the National Stuttering Association
5. Researchers create drug to keep tumor growth switched off
6. Urine protein test might help diagnose kidney damage from lupus, UT Southwestern researchers find
7. GUMC researchers say flower power may reduce resistance to breast cancer drug tamoxifen
8. Clemson researchers develop hands-free texting application
9. Researchers find biomarkers in saliva for detection of early-stage pancreatic cancer
10. Researchers chart genomic map spanning over 2 dozen cancers
11. Researchers discover second protective role for tumor-suppressor
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... PurhealthRX , a leading Health and Nutrition ... the Purzorb™process to full spectrum CBD oil will revolutionize the rapidly growing CBD market ... can be easily incorporated into liquid products, while reducing costs to end users. , ...
(Date:10/13/2017)... OBISPO, Calif. (PRWEB) , ... October 13, 2017 , ... ... or dementia. However, many long-term care insurance companies have a waiver for care if ... the 90-day elimination period, when the family pays for care, is often waived, so ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at The ... the most popular and least understood books in the Holy Scriptures, Revelation. The Book ... have baffled scholars for centuries. Many have tossed it off as mere rubbish, but ...
(Date:10/13/2017)... ... ... “America On The Brink”: the Christian history of the United States and the loss ... author, William Nowers. Captain Nowers and his wife, Millie, have six children, ten ... the Navy. Following his career as a naval aviator and carrier pilot, he ...
(Date:10/12/2017)... ... October 12, 2017 , ... The ... demand of today’s consumer and regulatory authorities worldwide. From Children’s to Adults 50+, ... to meet the highest standard. , These products are also: Gluten Free, ...
Breaking Medicine News(10 mins):
(Date:9/25/2017)... , Sept. 25, 2017   Montrium ... Master File solutions, today—from the IQPC Trial Master ... , NL)—announced that EastHORN Clinical Services has ... clinical programs and TMF management. EastHORN, a leading ... eTMF platform to increase transparency to enable greater ...
(Date:9/22/2017)... AVACEN Medical (AVACEN) announced that its CE-Marked ... those with the widespread pain associated with fibromyalgia in ... Essex, England commented, "I had ... no sleep at all, tremendous pain, with every movement ... [the AVACEN 100] enough, how this has and is ...
(Date:9/18/2017)... R.I. , Sept. 18, 2017 /PRNewswire/ ... the fields of bioinformatics and immune engineering, ... a protective avian influenza A (H7N9) vaccine. ... distantly related to seasonal influenza and presents ... rely on prior exposure to be effective. ...
Breaking Medicine Technology: