Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Designer biosensor can detect antibiotic production by microbes


Researchers from North Carolina State University have engineered designer biosensors that can detect antibiotic molecules of interest. The biosensors are a first step toward creating antibiotic-producing "factories" within microbes such as E. coli.

Macrolides are a group of naturally occurring small molecules that can have antibiotic, antifungal or anticancer effects. The antibiotic erythromycin is one example - it is a macrolide produced by soil-dwelling bacteria.

This is MphR biosensor binding to its target DNA sequence.

Credit: Edward Kalkreuter

Researchers are interested in using these natural antibiotics and the microbes that produce them in order to develop new antibiotics; however, microbes that produce antibiotic macrolides only make small amounts of a limited variety of antibiotics.

"Our ultimate goal is to engineer microbes to make new versions of these antibiotics for our use, which will drastically reduce the amount of time and money necessary for new drug testing and development," says Gavin Williams, associate professor of bio-organic chemistry at NC State and corresponding author of a paper describing the research.

"In order to do that, we first need to be able to detect the antibiotic molecules of interest produced by the microbes."

Williams and his team used a naturally occurring molecular switch - a protein called MphR - as their biosensor. In E. coli, MphR can detect the presence of macrolide antibiotics being secreted by microbes that are attacking E. coli. When MphR senses the antibiotic, it turns on a resistance mechanism to negate the antibiotic's effects.

The researchers created a large library of MphR protein variants and screened them for the ability to switch on production of a fluorescent green protein when they were in the presence of a desired macrolide. They tested the variants against erythromycin, which MphR already recognizes, and found that some of the MphR variants improved their detection ability tenfold. They also successfully tested the variants against macrolides that were not closely related to erythromycin, such as tylosin.

"Essentially we have co-opted and evolved the MphR sensor system, increasing its sensitivity in recognizing the molecules that we're interested in," says Williams.

"We know that we can tailor this biosensor and that it will detect the molecules we're interested in, which will enable us to screen millions of different strains quickly. This is the first step toward high-throughput engineering of antibiotics, where we create vast libraries of genetically modified strains and variants of microbes in order to find the few strains and variants that produce the desired molecule in the desired yield."

The research appears in ACS Synthetic Biology, and was funded by the National Institutes of Health (grant GM104258) and the NC State Chancellor's Innovation Fund. Graduate student Yiwei Li, former graduate student Christian Kasey, former undergraduate student Mounir Zerrad, and T. Ashton Cropp, professor of chemistry at Virginia Commonwealth University, contributed to the work.


Note to editors: An abstract of the paper follows.

"Development of transcription factor-based designer macrolide biosensors for metabolic engineering and synthetic biology"

Authors: Christian Kasey, Mounir Zerrad, Yiwei Li, Gavin Williams, North Carolina State University; Ashton Cropp, Virginia Commonwealth University

Published: ACS Synthetic Biology

DOI: 10.1021/acssynbio.7b00287


Macrolides are a large group of natural products that display broad and potent biological activities and are biosynthesized by type I polyketide synthases (PKSs) and associated enzymatic machinery. There is an urgent need to access macrolides and unnatural macrolide derivatives for drug discovery, drug manufacture, and probe development. Typically, efforts to engineer the biosynthesis of macrolides and macrolide analogues in various microbial hosts are hampered by the complexity of macrolide biosynthetic pathways and our limited ability to rationally reprogram type I PKSs and post-PKS machinery. High-throughput approaches based on synthetic biology and directed evolution could overcome this problem by testing the function of large libraries of variants. Yet, methods that can identify mutant enzymes, pathways, and strains that produce the desired macrolide target are not generally available. Here we show that the promiscuous macrolide sensing transcription factor MphR is a powerful platform for engineering variants with tailored properties. We identified variants that displayed improved sensitivity towards erythromycin, tailored the inducer specificity, and significantly improved sensitivity to macrolides that were very poor inducers of the wild-type MphR biosensor. Designer macrolide biosensors should find broad utility and enable applications related to high throughput synthetic biology and directed evolution of macrolide biosynthesis.

Media Contact

Tracey Peake


Tracey Peake | EurekAlert!

More articles from Life Sciences:

nachricht Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

Don't Give the Slightest Chance to Toxic Elements in Medicinal Products

23.03.2018 | Life Sciences

Sensitive grip

23.03.2018 | Materials Sciences

No compromises: Combining the benefits of 3D printing and casting

23.03.2018 | Process Engineering

Science & Research
Overview of more VideoLinks >>>