Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

When the going gets tough, slime molds start synthesizing

15.08.2006
In times of plenty, the uni-cellular slime mold Dictyostelium discoideum leads a solitary life munching on bacteria littering the forest floor. But these simple creatures can perform heroic developmental acts: when the bacterial food supply dries up, Dictyostelium amebas band together with their neighbors and form a multi-cellular tower designed to save the children.

In a forthcoming study in Nature Chemical Biology, investigators at the Salk Institute for Biological Studies and the Medical Research Council of Molecular Biology (MRC) in Cambridge, England, use traditional and computer-based methods to show how Dictyostelium synthesizes the chemical signal called DIF-1, short for Differentiation Inducing Factor, required for this developmental transformation.

The collaboration, explains co-senior author Joe Noel, Ph.D, a Howard Hughes Medical Institute investigator at Salk, "shows the power of a combined approach involving bioinformatics, enzymology, structural biology and genetics to get at the heart of why organisms exploit natural chemicals to survive and prosper in challenging ecosystems."

When slime molds starve, they collectively form a multicellular slug-like creature that locomotes en masse to a warm spot. There, in response to the DIF-1 signal, slugs literally stand up and their cells metamorphose into either a column of stalk cells or next-generation spore cells, which perch atop the column waiting for food supplies to be restored.

Noel and Michael Austin, Ph.D., a postdoctoral fellow in Noel's lab and co-lead author of the study, have an ongoing interest in the biosynthesis of diverse plant and microbial polyketides by enzymes known as type III PKSs. Plants make polyketide natural products such as flavonoids and stilbenes for use as sunscreens, antibiotics, flower pigments, and anti-oxidants. Explains Austin, "Plant polyketides are also increasingly recognized to have significant benefits in the human diet as health-promoting components of green tea, red wine, and soybeans."

Turns out, DIF-1 belongs to the same crowd. "While reading a review article on the diversity of polyketides in the journal Nature, we realized that the core chemical structure of DIF-1, an important developmental signal in Dictyostelium, is similar to natural products made by plant type III PKSs," recalls Austin.

At the time, Dictyostelium was in the midst of having its genome sequenced, and the bits and pieces of raw DNA sequencing data were being deposited in publicly available databases. Austin recalled, "One night I performed a bioinformatics search to look for genetic evidence that would suggest the existence of a type III PKS in Dictyostelium." Using various computer programs to find, assemble, and translate in silico the relevant raw DNA sequencing fragments first into genes then into the proteins these genes encode, Austin reconstructed two type III PKS-like gene sequences, and also found a surprise.

Unexpectedly, these deduced genetic blueprints for type III PKSs revealed each Dictyostelium type III PKS to be fused to other enzymatically active protein domains. This never seen before hybrid arrangement works like a very efficient bucket brigade that synthesizes polyketide molecules in slime mold cells.

"Nature has paved the way to exploit this novel domain arrangement to bioengineer more efficient ways of making modified polyketides for human uses," said Austin.

Moving to the bench, Austin and Noel lab manager Marianne Bowman isolated Dictyostelium DNA encoding the type III PKS domains and not only determined their structure, which indeed resembled a plant PKS, but also showed that one of them, called Steely2, made the chemical scaffold of DIF-1 in a test tube. All that was left was to prove was that slime molds themselves used the newly discovered enzyme to make DIF-1.

For that Noel and Austin turned to co-senior author Robert Kay, Ph.D., a Dictyostelium cellular differentiation expert and groupleader at the MRC. "We wrote a paper and sent a version to Rob Kay and said, 'You don't know us, but here's what we do. Biochemically we have identified the machinery that makes the essential precursor for the bioactive DIF-1 molecule.' "

Kay replied that he and co-lead author Tamao Saito, PhD., a scientist on sabbatical in his lab, had also focused on these unusual type III PKS genes following the recently completed final assembly and annotation of the entire Dictyostelium genome, which was carried out by a worldwide collaboration of many scientists, including the Kay group.

Working independently, Saito and Kay had deleted the Dictyostelium gene for Steely2. Not only could the resulting "deficient" slime molds not make DIF-1 but they couldn't construct the rescue tower, which was exactly the biological corroboration that the Noel lab wanted to hear. The two labs pooled data and now publish their work as one, very complete story while continuing to collaborate on the chemical diversity found in this fascinating organism that crawls around on the forest floor.

Says Noel, who is a professor in the Jack H. Skirball Center for Chemical Biology and Proteomics at Salk, "This is a wonderful example of where egos get pushed aside about who did what and instead, as a scientific community, groups come together to address a fundamental question in biology. In the process, we collectively discovered an efficient chemical factory in Dicytostelium cells that informs us about how to modify similar systems used in other organisms to produce important medicines from nature."

For Noel the problem is to understand biocomplexity at a level traditionally ignored - the plethora of natural chemicals found throughout nature. Organisms use chemicals as a means of interacting with their surroundings and mankind has exploited this fact to discover the vast majority of pharmaceuticals used to treat disease today. "The major fundamental question in our case is why do organisms make chemicals, what role do these molecules play in nature and how does the cellular machinery used to make them evolve over millions of years to provide new ways for the host organisms to survive and prosper. Understanding the diversity of natural chemicals and the machinery that produces them gives us a window to look back in time and understand how organisms evolve at the molecular level."

Gina Kirchweger | EurekAlert!
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>