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Oct. 23, 2018

Scientists find new methods to control bacterial factories for biotech aims

Michigan State University scientists have announced a breakthrough in manipulating miniature factories, found in bacteria, that hold much promise in the biotech field.

The factories, or bacterial microcompartments, are widespread in nature and do different things depending on the host. For example, in cyanobacteria that harvest energy from the sun, they help to  construct high-energy compounds. In our own guts, pathogenic bacteria use the factories – because the processes they perform are inefficient outside of them and sometimes use toxic materials – to outcompete our good bacteria. 

Scientists want to retrofit the factories with new machines to perform designed functions. The synthetic versions could sustainably make biofuels, industrial materials and nanoscale medical devices. 

In a Nature Communications publication, the lab of Cheryl Kerfeld announces new methods to manipulate factories:

  • Complementation-based Affinity Purification, or CAP,: which quickly screens for the assembly and extraction of the factories
  • Encapsulation via Covalent-linkage, or EnCo,: which helps to predictably insert custom machinery in the factories

“Current technologies require many days to prepare and extract a synthetic factory shell," Andrew Hagen, a post-doc in the Kerfeld lab, said. "We also have had limited options to insert custom machinery in it. I wanted to develop better ways to do those two things.”

The factory walls are made of proteintiles, shaped like hexagons and pentagons, that snap together to form an enclosure that looks like a soccer ball. 

In the lab, scientists rely on chemical mixtures to make synthetic factories. And it is challenging to fish them out once they're completed. The new method shows an easier way to extract the factories:

  1. The team creates a factory that lacks one of the wall protein tiles.
  2. They add a tag to the missing tile.
  3. They add the tile back to the mixture, where it snaps into place when it finds the factories; 
  4. The team extracts the factory with the help of the tagged tile. The team attracts that tag with a system that works like Velcro.

The scientists also report a method to insert custom enzymes inside the factories. It relies on a new technology that works like protein super glue. 

“The technology has two entities, SpyTag and SpyCatcher, that are attracted to each other,” Andrew said. “We insert a SpyCatcher ‘docking site’ on the inside of a factory wall. We then add a SpyTag on the machinery. Once in the same environment, the SPY system comes together like glue.”

Once ‘glued’ to a factory, the machinery can’t get out. So far, the team has managed to insert 60 copies of a single enzyme into a factory. The team aims to increase that number, as one factory could ideally fit around 200 copies.

The current proof of concept is looking promising. Next is to realize some of the technology’s promise. One such application is to produce chemicals that are used in industry. For example, another team member is working on producing the molecule that gets turned into rubber, a process that usually needs fossil fuels. Other ideas include biofuels and medical tools.

“We also think other scientists can use these methods with different bacteria and their factories,” Andrew said. “There is a good chance they will adopt these new methods widely."