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:2/13/2017)... FRANCISCO , Feb. 13, 2017  RSA ... centralized platform that is designed to enhance fraud ... latest release in the RSA Fraud & Risk ... enable organizations to leverage additional insights from internal ... tools to better protect their customers from targeted ...
(Date:2/10/2017)... , Feb 10, 2017 Research ... report "Personalized Medicine - Scientific and Commercial Aspects" ... ... medicine. Diagnosis is integrated with therapy for selection of treatment ... early detection and prevention of disease in modern medicine. Biochip/microarray ...
(Date:2/8/2017)... , Feb. 8, 2017 About Voice Recognition ... to match it against a stored voiceprint template. ... pitch, cadence, and tone are compared to distinguish ... hardware installation, as most PCs already have a ... transactions. Voice recognition biometrics are most likely to ...
Breaking Biology News(10 mins):
(Date:2/16/2017)... DIEGO , Feb. 16, 2017  Dermata ... innovative products to treat a variety of dermatological ... million Series 1a financing and entered into a ... (SVB).  Dermata intends to use the capital for ... making major advancements in the treatment of serious ...
(Date:2/16/2017)... ... 2017 , ... AxioMed announced today the success of the ... completed the procedure on Monday, Jan. 30 at Andrews Memorial Hospital in Kingston, ... degenerative disc disease with radiculomyelopathy, as a result of degenerative cervical discs at ...
(Date:2/16/2017)... BOSTON , Feb. 16, 2017 /PRNewswire/ ... for rare genetic deficiencies that result in ... of a $41 million mezzanine round of ... Ipsen, OrbiMed, MPM Capital, New Enterprise Associates, ... an undisclosed public healthcare investment fund. Rhythm ...
(Date:2/16/2017)... ... February 16, 2017 , ... ... further extended its industry leading Biochemistry Services specifically targeting the rapidly growing ... and methods for the biochemical and biosimilar characterization , product-related impurity ...
Breaking Biology Technology: