Scientists use E. coli to make drugsDecember 23rd, 2008 - 1:13 pm ICT by IANS
Washington, Dec 23 (IANS) Researchers have turned to the lethal E. coli to synthesise a class of natural products known as bacterial aromatic polyketides (BAP) that include antibiotic and anti-cancer drugs. BAPs include the antibiotic tetracycline and the compound doxorubicin, used in the treatment of breast and other cancers. Many of these natural products are synthesized by organisms that are difficult to collect, grow and maintain.
Accordingly, researchers turned to simpler organisms like E. coli, whose fast growth, variety of genetic tools and well-understood metabolism make it an ideal host for engineering and mass producing these compounds.
To achieve the successful synthesis of the aromatic polyketides, University of California Los Angeles (UCLA) research team of Yi Tang, associate professor and graduate students Wenjun Zhang and Yanran Li first dissected a polyketide synthase enzyme from a rice plant fungus, then reassembled it and transferred it into the E. coli bacterium.
The resulting synthetic enzyme is necessary to synthesize the carbon backbone of aromatic polyketides, which was previously inaccessible in E. coli.
Besides the synthetic enzyme, researchers introduced other enzymes to form a new pathway in E. coli that produced a range of bacterial aromatic polyketides from simple nutrients such as glucose, said an UCLA release.
The findings are scheduled for publication in the Dec 30 issue of the Proceedings of the National Academy of Sciences.
“This is a key advance in the field of natural product biosynthesis,” said Tang. “We have now outfitted E. coli with the ability to make this family of compounds that are vital toward treating diseases such as infectious diseases and cancer.
“Furthermore, we can now take advantage of the E. coli machinery to engineer the pathways we introduced and synthesize new versions of natural products that may be more potent than the current versions - so-called unnatural natural products.”
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Tags: antibiotic tetracycline, cancer drugs, carbon backbone, e coli bacterium, enzyme researchers, national academy of sciences, plant fungus, proceedings of the national academy of sciences, synthetic enzyme, ucla research