Synthesis of amino acids from carbon reaches 97% efficiency with cell-free system

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The building blocks of proteins, amino acids, are essential for all living things. Twenty different amino acids build the thousands of proteins that carry out biological tasks. While some are made naturally in our bodies, others are absorbed through the food we eat.

Amino acids also play a critical role commercially where they are manufactured and added to pharmaceuticals, dietary supplements, cosmetics, animal feeds, and industrial chemicals—an energy-intensive process leading to greenhouse gas emissions, resource consumption, and pollution.

A new system developed at Georgia Tech could lead to an alternative: a commercially scalable, environmentally sustainable method for amino acid production that is carbon negative, using more carbon than it emits.

The breakthrough builds on a method that the team pioneered in 2024 and solves a key issue—increasing efficiency to an unprecedented 97% and reducing the bioprocess cost by over 40%. It's the highest reported conversion of CO₂ equivalents into amino acids using any synthetic biology system to date.

Published in the journal ACS Synthetic Biology, the study, "Cell-Free-Based Thermophilic Biocatalyst for the Synthesis of Amino Acids From One-Carbon Feedstocks," was led by Bioengineering Ph.D. student Ray Westenberg and Professor Pamela Peralta-Yahya.

"This work shifts the narrative from simply reducing carbon emissions to actually consuming them to create value," says Peralta-Yahya. "We are taking low-cost carbon sources and building essential ingredients in a truly carbon-negative process that is efficient, effective, and scalable."

Heat-loving organisms

The work builds on the cell-free technology the team used in their earlier study. "Previously, we discovered that a system that uses the machinery of cells, without using actual living cells, could be used to create amino acids from carbon dioxide," Peralta-Yahya explains. "But to create a commercially viable system, we needed to increase the system's efficiency and reduce the cost."

The team discovered that bits of leftover cells were consuming starting materials, and—like a machine with unnecessary gears or parts—this limited the system's efficiency. To optimize their "machine," the team would need to remove the extra background machinery.

"Leftover cell parts were using key resources without helping produce the amino acids we were looking for," says Peralta-Yahya. "We knew that heating the system could be one way to purify it because heat can denature these components."

The challenge was in how to protect the essential system components from the high temperatures, she adds. "We wondered if introducing enzymes produced by a heat-loving bacterium, Moorella thermoacetica, might protect our system, while still allowing us to denature and remove that inefficient background machinery."

The results were astounding: After introducing the enzymes, heating and "cleaning" the system, and letting it cool to room temperature, synthesis of the amino acids serine and glycine leaped to 97% yield—nearly three times that of the team's previous system.

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Scaling for sustainability

To make the system viable for large-scale use, the team also needed to reduce costs. "One of the most costly components in this system is the cofactor tetrahydrofolate (THF)," Peralta-Yahya shares. "Reducing the amount of THF needed to start the process was one way to make the system more inexpensive and ultimately more commercially viable."

By linking reaction steps so waste from one step fueled the next, the team devised a method to recycle THF within the system that reduces the amount of THF needed by five-fold—lowering bioprocessing costs by 42%.

"This decrease in cost and increase in yield is a critical step forward in creating a method with real potential for use in industry and manufacturing," Peralta-Yahya says. "This system could pave the way for moving this carbon-negative technology out of the lab and onto the continuous, industrial scale."

Publication details

Ray Westenberg et al, Cell-Free-Based Thermophilic Biocatalyst for the Synthesis of Amino Acids from One-Carbon Feedstocks, ACS Synthetic Biology (2025). DOI: 10.1021/acssynbio.5c00352

Journal information: ACS Synthetic Biology

Provided by Georgia Institute of Technology