Coupled incremental precursor and co-factor supply improves 3-hydroxypropionic acid production in Saccharomyces...

Area of Science:

• Biotechnology
• Synthetic Biology
• Industrial Microbiology

Background:

• 3-Hydroxypropionic acid (3-HP) is a key platform chemical for producing acrylic acid and acrylamide.
• Current fermentative production of 3-HP primarily relies on bacterial systems, which have limitations for large-scale applications.
• Developing yeast-based fermentation offers a sustainable, potentially cost-effective alternative to petrochemical feedstocks.

Purpose of the Study:

• To evaluate the production of 3-HP in Saccharomyces cerevisiae using a malonyl-CoA dependent pathway.
• To engineer the yeast host strain for enhanced 3-HP production.
• To demonstrate the feasibility of yeast as a cell factory for bio-based 3-HP.

Main Methods:

• Engineered Saccharomyces cerevisiae to produce 3-HP via the malonyl-CoA pathway.
• Increased the intracellular availability of the precursor malonyl-CoA.
• Coupled 3-HP production with enhanced NADPH supply through metabolic engineering.

Main Results:

• Successfully demonstrated 3-HP production in yeast through the malonyl-CoA pathway.
• Achieved a five-fold improvement in 3-HP production.
• Reached a final titer of 463 mg/L of 3-HP.
• Enabled low-pH fermentation, reducing overall process costs.

Conclusions:

• Yeast, specifically Saccharomyces cerevisiae, can be engineered as an effective cell factory for 3-HP production.
• The malonyl-CoA pathway in yeast offers a viable route for sustainable bio-based chemical manufacturing.
• This work opens avenues for future production of 3-HP and its derivatives using yeast platforms.