Advances in metabolic engineering and fermentation for 3-hydroxypropionic acid biosynthesis: a comprehensive review

Area of Science:

• Biotechnology and Bioengineering
• Metabolic Engineering
• Industrial Microbiology

Background:

• The transition to biobased manufacturing requires sustainable and economical conversion of biomass into valuable chemicals.
• 3-hydroxypropionic acid (3-HP) is a versatile platform molecule with applications in bioplastics and other derivatives, making it a key target for biobased production.

Purpose of the Study:

• To review recent advancements in microbial 3-HP production.
• To analyze strategies for overcoming metabolic and process limitations.
• To highlight innovations for scalable and sustainable 3-HP biomanufacturing.

Main Methods:

• Advanced strain engineering and pathway rewiring.
• Cofactor optimization and metabolic modeling, including flux balance analysis.
• Tolerance engineering and dynamic regulation of metabolic flux.

Main Results:

• Strategies to mitigate byproduct formation, improve redox balance, and enhance cellular tolerance have been identified.
• Emerging approaches like dynamic flux regulation and co-production pathways show potential for increased yields and robustness.
• Fermentation innovations focus on improving productivity, substrate efficiency, and achieving industrially relevant titers.

Conclusions:

• Significant progress has been made in microbial 3-HP production through integrated approaches.
• Overcoming metabolic constraints and optimizing fermentation are crucial for scalability.
• These advancements pave the way for sustainable and economically viable biobased manufacturing of 3-HP.