Pilot-scale production of leucine from CO₂

Area of Science:

• Biotechnology
• Synthetic Biology
• Microbial Engineering

Background:

• Amino acids, like leucine, are vital compounds with broad applications in medicine, pharmaceuticals, cosmetics, food, and animal feed.
• Current production methods often rely on traditional fermentation or chemical synthesis, with varying economic and environmental impacts.
• The need for sustainable and efficient production of essential amino acids is growing.

Purpose of the Study:

• To engineer a novel archaeal cell factory for the production of leucine directly from carbon dioxide (CO2).
• To optimize the cell factory through rational design, random mutagenesis, and metabolic pathway engineering.
• To assess the bioprocess-technological performance, scalability, and economic feasibility of CO2-based leucine production.

Main Methods:

• Utilized rational design, random mutagenesis, and pathway engineering to develop an archaeal cell factory.
• Conducted bioprocess-technological examinations and scaled up the production process.
• Performed a 2-day fed-batch campaign at a 150-L pilot-plant scale.
• Carried out a comprehensive techno-economic analysis.

Main Results:

• Successfully generated an archaeal cell factory capable of producing leucine from CO2.
• Achieved a mean volumetric leucine productivity of 65 mg L^-1 h^-1.
• Produced 181 g of leucine from CO2 in a 150-L pilot-plant scale fed-batch campaign.
• Demonstrated high productivity, product quality, and operational stability.

Conclusions:

• The engineered archaeal cell factory offers a promising sustainable route for leucine production from CO2.
• The bioprocess is scalable and demonstrates high efficiency and stability.
• Techno-economic analysis suggests that CO2-based leucine production is nearly economically feasible on a global scale, paving the way for industrial application.