Featured Research

from universities, journals, and other organizations

Erythromycin A produced in E. coli for first time: Biosynthetic breakthrough paves way for other pharmaceuticals

Date:
November 26, 2010
Source:
Tufts University
Summary:
For the first time, researchers have made the antibiotic erythromycin A, and two variants, using E. coli as the production host. This is a cost-effective way to make erythromycin A and new drugs to combat antibiotic resistant pathogens. The E. coli host also offers next-generation engineering opportunities for other products with complex biosynthetic pathways.

Researchers at Tufts University School of Engineering have reported the first successful production of the antibiotic erythromycin A, and two variations, using E. coli as the production host.

The work, published in the November 24, 2010, issue of Chemistry and Biology, offers a more cost-effective way to make both erythromycin A and new drugs that will combat the growing incidence of antibiotic resistant pathogens. Equally important, the E. coli production platform offers numerous next-generation engineering opportunities for other natural products with complex biosynthetic pathways.

"We have now established E. coli as a viable option for making erythromycin A and as a platform for the directed production of erythromycin analogs. Our ability to fully manipulate erythromycin A's biosynthetic pathway to expand molecular diversity and antibiotic activity help sets a precedent for producing other similarly complex and medicinally relevant natural products," said lead researcher Blaine Pfeifer, Ph.D., assistant professor of chemical and biological engineering at Tufts.

Erythromycin A is a potent weapon in the treatment of bacterial infections. The bacterium Saccharopolyspora erythraea, which is found in the soil, naturally produces several variants of erythromycin. Erythromycin A is the most common and most biologically active.

Because of the challenges associated with engineering Saccharopolyspora erythraea, researchers have hoped to achieve the complete production of erythromycin A using E. coli. More than 20 enzymes must work in concert to create the erythromycin A molecule. This genetic and biochemical complexity makes synthesis notoriously hard. Previous research had reported manufacture of erythromycin A intermediates in E. coli but not the final product.

"To transfer and reconstitute these biosynthetic pathways is very difficult. In fact, erythromycin A poses nearly every challenge that must be addressed in the quest for complex heterologous biosynthesis of natural products," Pfeifer said.

He noted that the Tufts researchers followed a direction that was different from other groups. The Tufts team focused on reconstituting and ultimately manipulating the compound's original biosynthetic pathway rather than using analogous enzymes extracted from analogous pathways. The research team included Haoran Zhang, doctoral student in chemical engineering; Yong Wang, former postdoctoral associate now at East China University of Science & Technology; Jiequn Wu, a visiting doctoral student from East China University of Science & Technology, and Karin Skalina, a Tufts senior who is studying chemical engineering.

Pfeifer's work focuses on finding more efficient and cost-effective ways to engineer biological products, including antibiotics, anti-cancer agents and vaccines. The last 10 to 15 years have seen a growing commitment to the use of heterologous biosynthesis (in which genetic material is transferred to a more technically convenient host organism) in the production of antibiotics and other pharmaceuticals. Pfeifer and collaborators at MIT recently produced early intermediates of the anticancer agent Taxol using E. coli as a surrogate host.


Story Source:

The above story is based on materials provided by Tufts University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Haoran Zhang, Yong Wang, Jiequn Wu, Karin Skalina, Blaine A. Pfeifer. Complete Biosynthesis of Erythromycin A and Designed Analogs Using E. coli as a Heterologous Host. Chemistry and Biology, 2010; DOI: 10.1016/j.chembiol.2010.09.013

Cite This Page:

Tufts University. "Erythromycin A produced in E. coli for first time: Biosynthetic breakthrough paves way for other pharmaceuticals." ScienceDaily. ScienceDaily, 26 November 2010. <www.sciencedaily.com/releases/2010/11/101124124020.htm>.
Tufts University. (2010, November 26). Erythromycin A produced in E. coli for first time: Biosynthetic breakthrough paves way for other pharmaceuticals. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2010/11/101124124020.htm
Tufts University. "Erythromycin A produced in E. coli for first time: Biosynthetic breakthrough paves way for other pharmaceuticals." ScienceDaily. www.sciencedaily.com/releases/2010/11/101124124020.htm (accessed July 22, 2014).

Share This




More Plants & Animals News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

San Diego Zoo Welcomes New, Rare Rhino Calf

San Diego Zoo Welcomes New, Rare Rhino Calf

Reuters - US Online Video (July 21, 2014) An endangered black rhino baby is the newest resident at the San Diego Zoo. Sasha Salama reports. Video provided by Reuters
Powered by NewsLook.com
Shark Sightings a Big Catch for Cape Tourism

Shark Sightings a Big Catch for Cape Tourism

AP (July 21, 2014) A rise in shark sightings along the shores of Chatham, Massachusetts is driving a surge of eager vacationers to the beach town looking to catch a glimpse of a great white. (July 21) Video provided by AP
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
A Centuries' Old British Tradition Is Far from a Swan Song

A Centuries' Old British Tradition Is Far from a Swan Song

AFP (July 19, 2014) As if it weren't enough that the Queen is the Sovereign of the UK and 15 other Commonwealth realms, she is also the owner of all Britain's unmarked swans. Duration: 02:18 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins