Metabolic flux reprogramming and protein engineering drive efficient l-arginine biosynthesis

Area of Science:

• Metabolic Engineering
• Synthetic Biology
• Biotechnology

Background:

• Industrial l-arginine production faces challenges in metabolic regulation, pathway engineering, and fermentation optimization.
• Current methods limit efficient and coordinated biosynthesis for large-scale applications.

Purpose of the Study:

• To improve l-arginine (an amino acid) biosynthesis through metabolic reprogramming and enzyme engineering.
• To achieve high-titer, high-yield, and high-productivity l-arginine production in industrial fermentation.

Main Methods:

• Utilized an enzyme-constrained model (ec_iML1515) to identify key gene targets for l-arginine production.
• Performed metabolic reprogramming and engineered the argininosuccinate synthetase (ArgG) enzyme.
• Optimized fermentation conditions (temperature, pH) for enhanced l-arginine production.

Main Results:

• Developed strain Arg11 with an l-arginine titer of 114.18 g/L, a yield of 0.57 g/g, and productivity of 2.27 g/L/h.
• Reduced aspartate accumulation by 7.6-fold through metabolic engineering.
• Achieved the best reported performance for l-arginine production in a 3-m³ fermenter.

Conclusions:

• Metabolic reprogramming and targeted enzyme engineering significantly enhance l-arginine biosynthesis.
• The optimized strain and fermentation process represent a breakthrough in industrial l-arginine production.
• This study provides a robust framework for improving amino acid production in microbial systems.