Featured Research

from universities, journals, and other organizations

Researchers Reconstitute Enzyme That Synthesizes Cholesterol Drug Lovastatin

Date:
November 10, 2009
Source:
University of California - Los Angeles
Summary:
Researchers have for the first time, successfully reconstituted one of the most interesting but least understood enzymes in the highly reducing iterative polyketide synthases found in filamentous fungi. This enzyme is responsible for producing the cholesterol-lowering compound lovastatin. Lovastatin is a blockbuster drug used for lowering cholesterol in those with hypercholesterolemia, and thus helps to prevent cardiovascular disease.

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.

Related Articles


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."

The research was supported in part by a grant from the National Institutes of Health and a fellowship from the David and Lucille Packard Foundation.


Story Source:

The above story is based on materials provided by University of California - Los Angeles. The original article was written by Wileen Wong Kromhout. Note: Materials may be edited for content and length.


Cite This Page:

University of California - Los Angeles. "Researchers Reconstitute Enzyme That Synthesizes Cholesterol Drug Lovastatin." ScienceDaily. ScienceDaily, 10 November 2009. <www.sciencedaily.com/releases/2009/11/091103171721.htm>.
University of California - Los Angeles. (2009, November 10). Researchers Reconstitute Enzyme That Synthesizes Cholesterol Drug Lovastatin. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2009/11/091103171721.htm
University of California - Los Angeles. "Researchers Reconstitute Enzyme That Synthesizes Cholesterol Drug Lovastatin." ScienceDaily. www.sciencedaily.com/releases/2009/11/091103171721.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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