Navigation Links
UCLA researchers reconstitute enzyme that synthesizes cholesterol drug lovastatin
Date:11/3/2009

Researchers from the UCLA Henry Samueli School of Engineering and Applied Science have for the first time successfully reconstituted in the laboratory the enzyme responsible for producing the blockbuster cholesterol-lowering drug lovastatin.

The research, published Oct. 23 in the journal Science, could potentially lead to the development of other compounds with similarly beneficial effects.

The lovastatin-synthesizing enzyme is one of the most interesting but least understood of the polyketide synthases, which are found in filamentous fungi and which play a crucial role in the synthesis of "small molecule natural products" pharmacologically or biologically potent compounds produced by living organisms, many of which are the active ingredients in pharmaceuticals.

Commonly used antibiotics, such as tetracycline, are produced by polyketide synthases. Polyketides represent a class of 7,000 known structures, of which more than 20 are commercial drugs, including the immunosuppressant rapamycin, the antibiotic erythromycin and the anticancer drug doxorubicin.

"In this study, we studied the enzyme that makes a small-molecule precursor to lovastatin. And what's really different about this enzyme, compared to all other enzymes people have studied, is that this enzyme is extraordinarily large," said Yi Tang, associate professor of chemical and biomolecular engineering. "It's one of the largest enzymes ever to be reconstituted in a test tube. It is 10 times the size of most enzymes people study."

The enzyme used in Tang's study has seven active sites and catalyzes more than 40 different reactions that eventually result in an important precursor to lovastatin.

By understanding how this large assembly line works, Tang's team hopes to retune the assembly line to be able to produce other natural products something nature doesn't currently do.

"It's like having an assembly line with seven stations, and in one round you have to go through a combination of these seven stations. Remarkably, this enzyme uses the assembly line eight times to make this small molecule every time, it uses a different combination of the individual stations," Tang said. "So the large enzyme is programmed to utilize these stations differentially at every cycle, in different combinations, and now we can do it in a test tube."

Tang's team has been able to recapture all of the steps needed to make the lovastatin precursor molecule. And with this, Tang hopes they will be able to disrupt, tweak and change some of the steps to make slightly different molecules that can be just as beneficial.

"It's biosynthetic engineering of an assembly line to make a molecule that nature doesn't make," Tang said. "So our eventual goal, once we understand how the enzyme works, is to rationally manipulate the individual stations or manipulate how a set of stations is used in each iteration to generate new compounds that nature doesn't make that will result in new activities, new molecules."


'/>"/>

Contact: Wileen Wong Kromhout
wwkromhout@support.ucla.edu
310-206-0540
University of California - Los Angeles
Source:Eurekalert

Related biology news :

1. Researchers identify proteins involved in new neurodegenerative syndrome
2. Texas researchers and educators head for Antarctica
3. MGH researchers describe new way to identify, evolve novel enzymes
4. University of Pennsylvania researchers develop formula to gauge risk of disease clusters
5. U of MN researchers discover noninvasive diagnostic tool for brain diseases
6. U of Minnesota researchers discover noninvasive diagnostic tool for brain diseases
7. Researchers discover new strategies for antibiotic resistance
8. Researchers find new taste in fruit flies: carbonated water
9. Binghamton University researchers investigate evolving malaria resistance
10. UIC researchers find promising new targets for antibiotics
11. Researchers develop simple method to create natural drug products
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/21/2016)... British Columbia , June 21, 2016 /PRNewswire/ ... appointed to the new role of principal product ... been named the director of customer development. Both ... NuData,s chief technical officer. The moves reflect NuData,s ... teams in response to high customer demand and ...
(Date:6/9/2016)... , June 9, 2016 ... deploy Teleste,s video security solution to ensure the safety of ... during the major tournament Teleste, an ... systems and services, announced today that its video security solution ... to back up public safety across the country. The ...
(Date:6/2/2016)... LONDON , June 2, 2016 ... Systems, Manned Platforms, Unmanned Systems, Physical Infrastructure, Support & ... intelligence provider visiongain offers comprehensive analysis of ... that this market will generate revenues of $17.98 billion ... Systems acquired DVTEL Inc, a leader in software and ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... , June 27, 2016  Sequenom, Inc. (NASDAQ: ... enabling healthier lives through the development of innovative products ... the United States denied its ... the claims of Sequenom,s U.S. Patent No. 6,258,540 (",540 ... criteria established by the Supreme Court,s Mayo Collaborative Services ...
(Date:6/27/2016)... -- Liquid Biotech USA , Inc. ... Research Agreement with The University of Pennsylvania ("PENN") ... patients.  The funding will be used to assess ... outcomes in cancer patients undergoing a variety of ... to support the design of a therapeutic, decision-making ...
(Date:6/24/2016)... ... 24, 2016 , ... Researchers at the Universita Politecnica delle Marche in Ancona ... or pleural mesothelioma. Their findings are the subject of a new article on the ... are signposts in the blood, lung fluid or tissue of mesothelioma patients that can ...
(Date:6/23/2016)... 2016 A person commits a crime, and the ... track the criminal down. An outbreak of foodborne ... Administration (FDA) uses DNA evidence to track down the bacteria ... far-fetched? It,s not. The FDA has increasingly used a complex, ... foodborne illnesses. Put as simply as possible, whole genome sequencing ...
Breaking Biology Technology: