Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Molecular level discovery could play role in development of new antibiotics


Chemists at the University of Illinois at Urbana-Champaign have uncovered the molecular activity of an enzyme responsible for naturally turning a small protein into a potent antibiotic known as a lantibiotic.

The finding is described in the Jan. 30 issue of the journal Science. The research details how the enzyme performs two biosynthetic reactions that lead to the formation of fused cyclic structures required for antimicrobial activity. The discovery unlocks a door that could lead to a new line of antibiotic compounds based on nature’s machinery, said Wilfred A. van der Donk, a professor of chemistry at Illinois.

The work was done using lacticin 481, a lantibiotic produced by one of several strains of Lactococcus lactis, a bacterium used in cheese production. Other lantibiotics are used to preserve other dairy products and canned vegetables. The lantibiotic nisin has been used for more than 50 years as an alternative to chemicals in food preservation in more than 40 countries without the development of significant antibiotic resistance.

"The use of antibiotics is an important area of medicine, because pathogenic bacteria are always in the environment," van der Donk said. "It’s important to renew our arsenal of compounds that combat pathogens. With the development of resistance -- not just the kind that occurs through evolution but also the kind potentially created in biological weapons by terrorists -- we will always need new antibiotics."

The breakthrough in van der Donk’s lab came in March 2003, when his doctoral student Lili Xie, now at the Harvard Medical School, noticed catalytic activity in the material she was investigating. Van der Donk had been pursuing such activity for six years. Many other labs have tried since the late 1980s, when the genes involved in nisin’s biosynthetic pathway were sequenced, but efforts to make analogs in vitro had failed.

Lantibiotics are ribosomally synthesized and modified into a bacteria-fighting form after translation. One type of lantibiotics is modified by two proteins, while another type, scientists have proposed, is able to complete the transformation, forming cyclic regions with sturdy protease-resistant bonds at precise locations, with just one enzyme.

The finding in van der Donk’s lab and subsequent analyses in the research laboratory of Neil L. Kelleher, a professor of chemistry and co-principal investigator, confirms that one enzyme, LctM, alone can complete the modification.

The researchers were led to LctM, which is involved in the biosynthesis of lacticin 481, through trial and error as they tried to manipulate a peptide substrate. LctM, acting in the presence of adenosine triphosphate and ionized magnesium, selected specific serines and threonines for modification, allowing for a correct final structure of the material.

It was reported in 1999 that lantibiotics such as nisin are effective and elude resistance because they work like a double-edged sword. They form holes in the cell membranes and also bind to intermediate targets of a disease-causing bacterium. Hitting on two targets simultaneously reduces the risk of resistance occurring, van der Donk said.

"We are interested in antibiotics that are used commercially and that are not chemically made but derived from organisms, such as bacteria, that make them for us," he said. "If nature makes these materials, wouldn’t it be great to understand and use the machinery that nature uses to make compounds ourselves? By having this purified system, we can modify the substrate of the enzyme that makes a lantibiotic and make antibiotic analogs that nature cannot make. This really opens an avenue to engineer antibiotics and look for active compounds that we can access using the machinery we’ve found."

The National Institutes of Health, Beckman Foundation and Burroughs Wellcome Fund supported the research through grants to van der Donk and Kelleher. Other contributors were research technician Olga Averin and doctoral students Leah M. Miller and Champak Chatterjee.

Jim Barlow | UIUC
Further information:

More articles from Life Sciences:

nachricht Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences

nachricht Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>