Biocatalytic synthesis of 2-fluoro-3-hydroxypropionic acid

Area of Science:

• Biotechnology
• Synthetic Chemistry
• Metabolic Engineering

Background:

• Fluorine incorporation enhances molecular properties for medicine, agriculture, and materials.
• Fluorinated compounds are valuable but rarely found in natural metabolic pathways.
• Expanding access to novel fluorinated molecules requires innovative synthetic strategies.

Purpose of the Study:

• To develop a novel biosynthetic pathway for producing 2-fluoro-3-hydroxypropionic acid (2-F-3-HP).
• To establish a biocatalytic method for synthesizing fluorinated organic compounds.
• To overcome limitations of traditional chemical synthesis for fluorinated molecules.

Main Methods:

• Engineered E. coli coexpressing methylmalonyl CoA synthase (MatBrp), methylmalonyl CoA reductase (MCR), and malonate transmembrane protein (MadLM).
• Whole-cell biotransformation for the synthesis of 2-F-3-HP.
• Utilized 2-F-3-HP as a substrate for synthesizing other fluorides, such as poly (2-fluoro-3-hydroxypropionic acid) (FP3HP).

Main Results:

• Successfully synthesized 2-F-3-HP using engineered E. coli.
• Achieved a concentration of 50.0 mg/L of 2-F-3-HP via whole-cell transformation within 24 hours.
• Demonstrated the potential of 2-F-3-HP as a precursor for other fluorinated compounds.

Conclusions:

• A novel, entirely biocatalytic method for producing 2-F-3-HP was established.
• This biosynthetic approach offers significant environmental and safety advantages over chemical synthesis.
• The developed strategy expands the toolkit for creating novel fluorinated molecules.