Navigation Links
E. coli engineered to produce important class of antibiotic, anti-cancer drugs
Date:12/22/2008

Researchers from the UCLA Henry Samueli School of Engineering and Applied Science have taken a major step forward in the field of metabolic engineering, successfully using the bacterium Escherichia coli to synthesize a class of natural products known bacterial aromatic polyketides, which include important antibiotic and anticancer drugs.

Natural products are pharmacologically or biologically potent chemical compounds produced by living organisms; many are the active ingredients in pharmaceuticals. Bacterial aromatic polyketides include the antibiotic tetracycline and the compound doxorubicin, used in the treatment of breast and other cancers.

Because many of these natural products are synthesized by organisms that are difficult to collect, grow and maintain, researchers have sought to produce them using 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.

While turning E. coli into a microbial factory for natural products has been highly successful, resulting in the production of groups of drugs that include antibiotics like erythromycin and vancomycin, as well as terpenes and alkaloids, attempts to synthesize bacterial aromatic polyketides had previously been hindered by the compounds' complicated assembly process.

To achieve the successful synthesis of the aromatic polyketides, the UCLA research team which included principal investigator Yi Tang, an associate professor of chemical and biomolecular engineering, 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.

In addition to the synthetic enzyme, the 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.

"This is a key advance in the field of natural product biosynthesis," said Tang of the research, which will be published Dec. 30 in Proceedings of the National Academy of Sciences and is currently available on the journal's website. "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."

On a more fundamental level, the UCLA researchers are exploring interactions between the bacterial and fungal components they introduced into E. coli, which are from different kingdoms of life.

"There are some beliefs that bacterial and fungal enzymes will not cross-talk to each other," said Zhang, the paper's lead author. "Our work showed that polyketide synthase from the two kingdoms can indeed be functionally combined inside the E. coli platform. Therefore, there is much to learn about why these interactions are possible."


'/>"/>

Contact: Matthew Chin
mchin@support.ucla.edu
310-206-0680
University of California - Los Angeles
Source:Eurekalert

Related medicine news :

1. Data from Patient Subsets of e-HEALING, a Worldwide Registry, Support Use of OrbusNeichs Genous(TM) Bio-Engineered R Stent(TM) as Alternative to Drug- Eluting Stents
2. T vs. B: Re-engineered human T cells effectively target and kill cancerous B cells
3. 5,000 Patients Treated With OrbusNeichs Genous(TM) Bio-engineered R Stent(TM) Now Enrolled in Real-Life Use Global Registry
4. Nanomedicine system engineered to enhance therapeutic effects of injectable drugs
5. Reconstructing mandibular defects with bioengineered tooth and bone
6. Symposium at Angioplasty Summit TCT Asia Pacific 2008 Features OrbusNeichs Genous(TM) Bio-engineered R stent(TM)
7. OrbusNeich Receives Approval to Market Genous(TM) Bio-engineered R stent(TM) in Taiwan
8. Tumor suppressor genes speed up and slow down aging in engineered mouse
9. FDA Proposes Regulations for Genetically Engineered Animals
10. Top Athletes Join Forces for a New Mission: Athlete-Engineered Skincare to Support Performance and Benefit Charity
11. Whiplash may produce delayed jaw pain
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... The International Association ... standards of excellence for the field of eating disorders, announces the opening of ... 2018 in Orlando, Florida at the Omni Resort at ChampionsGate. , ...
(Date:10/13/2017)... LUIS OBISPO, Calif. (PRWEB) , ... October 13, 2017 , ... ... Alzheimer’s or dementia. However, many long-term care insurance companies have a waiver for care ... is the 90-day elimination period, when the family pays for care, is often waived, ...
(Date:10/13/2017)... ... October 13, 2017 , ... Talented ... the lowdown on sciatica in a new episode of "Success Files," which is ... events and innovation and investigates each subject in-depth with passion and integrity. , ...
(Date:10/12/2017)... ... October 12, 2017 , ... CitiDent and San Francisco dentists, ... cutting-edge Oventus O2Vent technology. As many as 18 million Americans are estimated to ... breathing. Oral appliances can offer significant relief to about 75 percent of people ...
(Date:10/12/2017)... ... 12, 2017 , ... Asante, a nationally recognized health system ... their existing home health joint venture through an agreement, effective October 1, 2017, ... venture home health company with Asante, delivering clinically integrated care, for the past ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... 2, 2017  Eli Lilly and Company (NYSE: ... the third quarter of 2017 on Tuesday, October 24, ... that day with the investment community and media to ... conference call will begin at 9 a.m. Eastern time. ... live webcast of the conference call through a link ...
(Date:10/2/2017)... -- Halo Labs announces the European launch of their new low ... MIBio 2017 in Cambridge, U.K on October ... biopharmaceutical samples with unprecedented speed and sensitivity while using far less ... Imaging. ... analysis system ...
(Date:9/28/2017)... 2017 Hill-Rom Holdings, Inc. (NYSE: HRC), will ... and webcast on Friday, November 3, 2017, beginning at ... at approximately 8:30 a.m. (CDT) / 9:30 a.m. (EDT). ... financial performance and guidance for 2018, Hill-Rom executives will ... operational performance, and long-range financial outlook through 2020. ...
Breaking Medicine Technology: