Imagine if building new medicines or sustainable materials were as straightforward as snapping together LEGO® bricks. That’s the goal of a new project led by the Georgia Institute of Technology that could help transform the future of biomanufacturing.

The project, headed by Professor Mark Styczynski in Georgia Tech’s School of Chemical and Biomolecular Engineering (ChBE@GT), recently received a $9.2 million grant from the National Science Foundation Directorate for Technology, Innovation and Partnerships (NSF TIP) to accelerate the adoption of cell-free systems in biomanufacturing.

Promising Technology

Biotechnology has largely relied on living cells for production of products such as medicines, fragrances, or renewable fuels. But working with living cells can be complex and expensive.

Cell-free systems, by contrast, strip biology down to its essential parts, the enzymes and molecules that carry out life’s chemical reactions. This can simplify and speed up biomanufacturing, making it easier to scale.

The challenge, Styczynski explained, is that most cell-free projects still require custom-built setups. “Right now, engineering biology is like reinventing the wheel for every application,” he said. “You have to figure out how all the parts fit together each time. We want to change that by making ready-to-use modules that work right out of the box.”

Styczynski’s project, called Meta-PURE (PUrified Recombinant Elements), will create eight standardized modules, each designed for a key function in cell-free systems, such as generating energy, producing proteins, or assembling complex molecules.

“Like interchangeable puzzle pieces, these modules can be mixed and matched to support different applications,” Styczynski said.

Demonstrating Uses

His team will demonstrate the system’s versatility by producing santalene (a plant-derived fragrance used widely in consumer products), GamS protein (a tool that can improve cell-free processes), and a bacteriophage (a virus that can be safely used in research and the development of new therapeutic treatments).

These examples highlight the technology’s potential across industries ranging from pharmaceuticals and agriculture to chemicals and sustainable materials.

“We want to make these tools so that someone in industry can create their molecule or product more quickly and efficiently, and get it out the door,” Styczynski said. 

“Right now, cell-free systems are mostly limited to high-value products because the cost is too high. The goal is to drive costs down and productivity up, so we can move closer to commodity chemicals like biofuels or monomers for polymers, not just niche applications. One of our partners recently developed a butanol process that shows where this can go,” he said.

NSF Initiative

Styczynski’s team is one of four recently awarded an inaugural investment of $32.4 million to help grow the U.S. bioeconomy. The initiative is called the NSF Advancing Cell-Free Systems Toward Increased Range of Use-Inspired Applications (NSF CFIRE).

“NSF is resolute in our commitment to advancing breakthroughs in biotechnology, advanced manufacturing, and other key technologies of significance to the U.S. economy,” said Erwin Gianchandani, assistant director for NSF TIP. “The novel approaches from these four CFIRE teams will speed up and expand the adoption of cell-free systems across a variety of industries and ensure America’s competitive position in the global bioeconomy.”

Collaborative Effort

While ChBE@GT is the lead, Meta-PURE is a broad collaboration with partners across academia, industry, and government. Co-principal investigators include Paul Opgenorth, co-founder and vice president of development at the biotech firm eXoZymes; Nicholas R. Sandoval, associate professor of Tulane University’s Department of Chemical and Biomolecular Engineering; and Anton Jackson-Smith, founder of the biotech startup b.next.

Meta-PURE will also train graduate students and postdocs in partnership with industry, government, and other universities, helping prepare trainees to be the future of a highly interdisciplinary U.S. bioeconomy. The team will also engage the scientific community on the implementation of metrics and standards in cell-free biotechnology to better facilitate broad adoption and interoperability of not just the results of the Meta-PURE project, but of cell-free efforts more broadly.