Researchers from The University of Manchester have developed a common gut bacterium to produce a new category of antibiotics with the help of robotics. These antibiotics, called class II polyketides, are also naturally made by soil bacteria and possess antimicrobial properties which are important in the modern pharmaceutical industry to fight infectious diseases and cancer.
The naturally created Escherichia coli bacteria are hard to work with as they grow in thick clumps that do not work well with the automated robotic systems used for contemporary biotechnology research. By shifting the production machinery from the soil bacteria into E. coli, the Manchester researchers are now making this category of antibiotics accessible for much more speedy exploration.
This innovation could be crucial for the continuing fight against antimicrobial resistance, as recently designed automated robotics systems can at the moment be used to produce new antibiotics in quickly and efficiently.
In this work, reported in the journal PLOS Biology, the team guided by Professor Takano at The University of Manchester demonstrates the potential of this method. By integrating the bacterial production machinery with enzymes from fungi and plants, it was possible to create new chemical compounds not formerly observed in nature.
Using this plug-and-play system, it will at present be possible to investigate and engineer polyketides using robotic systems to create new and diversified polyketides in an automated, fast, and versatile manner.
Eriko Takano, Professor of Synthetic Biology said, “Nature is a huge treasure trove for powerful chemical compounds to treat a wide range of diseases. However, the most interesting chemicals often come from organisms that are difficult to work with in the laboratory.”
This has been a major bottleneck for our work on type II polyketides, a group of important chemicals, which are mostly produced by soil bacteria and other microorganisms that are challenging to grow. By successfully moving the production machinery for these compounds into the ‘laboratory workhorse’ bacterium E. coli, we can finally produce and engineer type II polyketides in our rapid robotic systems.
Eriko Takano, Professor of Synthetic Biology, The University of Manchester
Eriko Takano continues, “This not only allows us to trial new polyketides in an automated manner, but we will also be able to quickly rewrite the DNA sequences of the antibiotic biosynthesis pathways and combine them with new components from other organisms, such as medicinal plants and fungi, to produce variations on the antibiotic theme—including compounds that are not produced by the natural pathways, but may have enhanced or novel activities in the treatment of important diseases.”
Creating and testing 10 new potential antibiotics could take a person an entire year, but this automated robotic platform can make thousands within that time. This would vastly reduce the time it takes for new antibiotics to get to patients, and provide the essential agility to react to new outbreaks and pathogen strains.