The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production

Area of Science:

• Biotechnology
• Metabolic Engineering
• Chemical Synthesis

Background:

• 3-Hydroxypropionic acid (3-HP) is a valuable chemical precursor with significant industrial potential.
• Acetyl-CoA carboxylase (Acc) is a key enzyme in 3-HP biosynthesis via the malonyl-CoA pathway, but its toxicity limits production.
• Balancing Acc and malonyl-CoA reductase (MCR) expression is crucial for efficient 3-HP synthesis.

Purpose of the Study:

• To develop a strategy to mitigate Acc toxicity and enhance 3-HP production.
• To optimize the expression of Acc subunits (AccBC and DtsR1) for improved cell growth and 3-HP yield.
• To balance Acc and MCR expression for maximizing 3-HP production through the malonyl-CoA pathway.

Main Methods:

• Engineered microbial strains by adjusting Acc subunits (AccBC and DtsR1) expression to reduce toxicity.
• Balanced the expression of Acc and malonyl-CoA reductase (MCR) in engineered strains.
• Performed shake-flask and fed-batch fermentation to evaluate 3-HP production efficiency.

Main Results:

• Adjusting DtsR1 and AccBC expression accelerated cell growth and 3-HP production.
• Engineered strains achieved a titer of 6.8 g/L with a yield of 0.566 g/g glucose in shake-flask fermentation.
• Fed-batch fermentation yielded a high titer of 38.13 g/L, productivity of 1.03 g/L/h, and yield of 0.246 g/g glucose.

Conclusions:

• Mitigating Acc toxicity through expression adjustment is effective for enhancing 3-HP production.
• Balancing Acc and MCR expression represents a key strategy for maximizing 3-HP synthesis via the malonyl-CoA pathway.
• The developed strain is highly efficient for 3-HP production from inexpensive carbon sources, with potential for other malonyl-CoA derived compounds.