Metabolic engineering Corynebacterium glutamicum for D-chiro-inositol production

Area of Science:

• Biotechnology
• Metabolic Engineering
• Microbial Fermentation

Background:

• D-chiro-inositol (DCI) is a valuable compound with therapeutic potential for type II diabetes and polycystic ovary syndrome.
• Efficient microbial synthesis of DCI is crucial for its pharmaceutical applications.

Purpose of the Study:

• To engineer a Corynebacterium glutamicum strain for high-yield DCI production.
• To optimize fermentation conditions for maximizing DCI titer.

Main Methods:

• Generated a chassis strain (DCI-1) by knocking out inositol catabolism genes in C. glutamicum.
• Expressed various inosose isomerases and inositol dehydrogenase (IolG) in the chassis strain.
• Optimized fermentation parameters including pH, temperature, and substrate concentration.

Main Results:

• The engineered strain DCI-7, co-expressing IolI2 and IolG, achieved a DCI titer of 3.21 g/L with 20 g/L myo-inositol (MI).
• Further optimization led to a maximal DCI titer of 6.96 g/L under specific conditions (pH 8.0, 37°C, 40 g/L MI).
• This represents the highest reported DCI titer using whole-cell bioconversion.

Conclusions:

• The engineered C. glutamicum strain DCI-7 demonstrates a highly efficient and scalable method for DCI production.
• The achieved DCI titer significantly advances the potential for industrial-scale synthesis of this therapeutic compound.