Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Create New Method for Uncovering Natural Products from Mystery 'Orphan Genes'

29.01.2007
Approach leads to identification of compound with potential benefits in agriculture through crop protection

Microorganisms have a proven track record for producing powerful molecules useful in antibiotics, as anticancer agents and in treating human diseases.At times, researchers studying the genomes of these microorganisms have come across sections of DNA for which scientists cannot determine what is ultimately produced. It's not clear what might be created from these so-called "orphan gene clusters" and if those end products might carry beneficial qualities.

Scientists at Scripps Institution of Oceanography at UC San Diego have devised a new method for identifying the mysterious products of orphan gene clusters.

"In this new age of genomics, microorganisms have even more capacity to make exotic natural product molecules than we ever realized," said William Gerwick, a professor in Scripps Oceanography's Center for Marine Biotechnology and Biomedicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego. "However, sometimes we don't know how to find these products. We can see them in the genomic information but we can't necessarily find the resulting organic substances."

The method developed by Gerwick and his colleagues employs a novel combination of genomic sequence analysis and isotope labeling. The new "genomisotopic approach" is described in the new issue of Chemistry & Biology as the journal's featured cover paper.

Gerwick says the key to the genomisotopic approach lies in the combined power of bioinformatics—computer programming to predict the proteins as well as the component building blocks they will use to make the new mystery product—with the ability to provide building blocks containing distinctive isotope labels to cultures producing the mystery compound. The microorganism assimilates the isotope-tagged precursors, incorporates them into the mystery compound, thus enabling the researchers to "find" the mystery compound simply by looking for the isotope signature. According to the paper, the approach represents a valuable complement to existing genome "mining" strategies.

"This technique allows us to methodically and with a very well-defined strategy figure out and isolate the compounds that are produced from those orphan gene clusters," said Gerwick. "With the genomisotopic approach we're mapping out a metabolic process. We're watching the incorporation of the amino acid into a more complex natural products structure and visualizing it at the end by a combination of mass spectrometry and nuclear magnetic resonance spectroscopy."

The genomisotopic approach was born out of a failed experiment in Gerwick's laboratory. A student had attempted to clone the biosynthetic gene cluster for a certain compound. The student sequenced a stretch of DNA that initially appeared promising as the correct gene cluster, but ultimately proved not to be.

"So with that big stretch of DNA we scratched our heads and wondered, if it didn't make the compound we thought it did, what did it make?" said Gerwick. "We brainstormed and thought we could come up with an approach for finding out."

In addition to describing the genomisotopic approach, the Chemistry & Biology paper describes the identification of a compound of a previously unknown natural product discovered through the new method. Gerwick and his colleagues applied the approach and found what is now known as orfamide A, a new natural product that may prove beneficial in agriculture and crop protection due to its potential in suppressing plant diseases.

Gerwick says the new approach will now be applied to various organisms derived from the ocean, including marine bacteria.

In addition to Gerwick, the paper's coauthors include Harald Gross (Scripps and Oregon State University), Virginia Stockwell (Oregon State University), Marcella Henkels (U.S. Department of Agriculture), Brian Nowak-Thompson (Northland College) and Joyce Loper (U.S. Department of Agriculture).

The study was funded by the National Institutes of Health and the Microbial Genomic Sequencing Program of the U.S. Department of Agriculture Cooperative State Research, Education and Extension Service.

Mario Aguilera | EurekAlert!
Further information:
http://www.ucsd.edu

Further reports about: approach compound genomisotopic microorganism

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>