Bacteria are widely used to manufacture proteins used in medicine and industry, but the bugs often bungle the job. Many proteins fall apart and get cut up inside the bacteria before they can be harvested. Others collapse into useless tangles instead of folding properly, as they must in order to function normally.
A research team led by James Bardwell, who is a professor of molecular, cellular and developmental biology and of biological chemistry, as well as a Howard Hughes Medical Institute investigator, at the University of Michigan, developed a way to coerce bacteria into making large quantities of stable, functional proteins. Then, in exploring why these designer bacteria were so successful, the scientists discovered the molecular helper, Spy.
The research is scheduled for online publication Feb.13 in the journal Nature Structural & Molecular Biology.
In the first phase of the research, the team designed biosensors that directly link protein stability to the antibiotic resistance of bacteria. When a poorly folded, unstable protein is inserted into the middle of the biosensor in a bacterium, it disrupts the bug's resistance to antibiotics. When the protein is stabilized, resistance is restored.
The researchers inserted a particularly unstable protein into Escherichia coli (E. coli), which forced the bacteria to either adapt by improving protein stability or die when exposed to antibiotics. Through a "directed evolution" experiment, in which the scientists selected colonies with increasing antibiotic resistance—and increasing protein stability—the team generated designer bacteria that produced up to 700 times more of the previously unstable protein.
"It is exciting to realize that if even bacteria are asked in the right way, they can come up with good solutions to hard problems," said postdoctoral fellow Shu Quan, who spearheaded the work.
In looking to see why the designer bacteria were so much better at producing proteins, the scientists found that the efficient microbes were making much more of a small protein called Spy. Further study showed that the cradle-shaped Spy aids in protein refolding and protects unstable proteins from being cut up or sticking to other proteins.
"Our work may usher in an era of designer bacteria that have had their folding environment customized so that they can now efficiently fold normally unstable proteins," Bardwell said.
The work was conducted in Bardwell's lab at U-M. Mirek Cygler's laboratory at McGill University solved the structure of the Spy protein. In addition to Bardwell, Quan and Cygler, the paper's authors are masters students Philipp Koldewey and Stephan Hofmann; undergraduate students Nadine Kirsch and Jennifer Pfizenmaier; postdoctoral research associates Tim Tapley, Linda Foit and Guoping Ren; associate professor Ursula Jakob and associate professor Zhaohui Xu; all of U-M; and Karen Ruane and Rong Shi of McGill University.
The researchers received funding from Howard Hughes Medical Institute and the Canadian Institutes of Health Research.
Nancy Ross-Flanigan | EurekAlert!
At last, butterflies get a bigger, better evolutionary tree
16.02.2018 | Florida Museum of Natural History
New treatment strategies for chronic kidney disease from the animal kingdom
16.02.2018 | Veterinärmedizinische Universität Wien
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).
Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
16.02.2018 | Information Technology
16.02.2018 | Health and Medicine
16.02.2018 | Physics and Astronomy