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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>