Harnessing the Biomanufacturing Potential of a Non-Model Microorganism

A new collaboration between LanzaTech and the Agile BioFoundry aims to expand the genetic engineering toolbox of a non-model microorganism, Clostridium autoethanogenum, opening doors to producing increasingly complex molecules. The project will target the production of isoprene, a chemical compound that is a precursor for rubber. 

LanzaTech’s team sought to collaborate with the Agile BioFoundry particularly for its capabilities and expertise. “We have complementary expertise and infrastructure that we can use in collaboration to advance the development of these tools, and to reduce the time needed to produce complex molecules in non-model organisms,” said Michael Köpke, Vice President of Synthetic Biology at LanzaTech. 

Non-model microorganisms, which haven’t been extensively studied, often have unique qualities that could have applications for biomanufacturing. However, they often lack basic genetic engineering tools that are needed to use these microorganisms to develop bioproducts. 

One of these microorganisms, C. autoethanogenum, is the focus of biotechnology company LanzaTech. Instead of sugar, this microorganism uses carbon oxides (CO and CO2) to produce chemicals of interest. Currently, LanzaTech is using this process to produce ethanol, but the company is also exploring the potential of using this microorganism to produce other molecules. 

“Because this is a non-model microorganism, we still face some barriers to exploring its full potential,” said Marilene Pavan, senior scientist at LanzaTech. “We need more synthetic biology tools to over-express enzymes and make modifications.” 

tires

The project’s target molecule, isoprene, has a broad application space. For example, it can be used to make synthetic tires.

“However, it’s currently only made from petroleum,” Köpke said. “So it would be very interesting to show that we can produce this at scale using our microorganism and the tools we’re going to develop with the Agile BioFoundry.”

This includes CRISPR tools that will allow researchers to modify this microorganism to improve the production of isoprene, as well as high-throughput screening tools using microfluidics. 

“Screening products is definitely a bottleneck for us,” Pavan said. “Usually, you need to have larger volumes of fermentation experiments to detect the products. We want to use microfluidics to decrease the volume and increase the number of samples we can test so we can screen the best production candidates.” 

Not only will these tools benefit C. autoethanogenum, but the team hopes they can be applied to other non-model microorganisms, opening up more opportunities for biomanufacturing.

“We want to guarantee the transferability of this knowledge and these tools and methods, so others can take advantage as well,” Pavan said. 

This collaboration between the Agile BioFoundry and industry is one of six projects totaling over $5 million announced this year by the U.S. Department of Energy to conduct research and development needed to accelerate the U.S. biomanufacturing sector. 

The Agile BioFoundry is funded by the U.S. Department of Energy Bioenergy Technologies Office