Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular level discovery could play role in development of new antibiotics

30.01.2004


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:
http://www.news.uiuc.edu/news/04/0129lantibiotics.html

More articles from Life Sciences:

nachricht Monitoring biodiversity with sound: how machines can enrich our knowledge
18.06.2019 | Georg-August-Universität Göttingen

nachricht Uncovering hidden protein structures
18.06.2019 | Universität Konstanz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

Im Focus: Tube anemone has the largest animal mitochondrial genome ever sequenced

Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.

The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....

Im Focus: Tiny light box opens new doors into the nanoworld

Researchers at Chalmers University of Technology, Sweden, have discovered a completely new way of capturing, amplifying and linking light to matter at the nanolevel. Using a tiny box, built from stacked atomically thin material, they have succeeded in creating a type of feedback loop in which light and matter become one. The discovery, which was recently published in Nature Nanotechnology, opens up new possibilities in the world of nanophotonics.

Photonics is concerned with various means of using light. Fibre-optic communication is an example of photonics, as is the technology behind photodetectors and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Uncovering hidden protein structures

18.06.2019 | Life Sciences

Monitoring biodiversity with sound: how machines can enrich our knowledge

18.06.2019 | Life Sciences

Schizophrenia: Adolescence is the game-changer

18.06.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>