Dynamic metabolic modelling predicts efficient acetogen-gut bacterium cocultures for CO-to-butyrate conversion

Area of Science:

• Microbial biotechnology
• Synthetic biology
• Metabolic engineering

Background:

• Acetogens naturally produce acetate, but engineering for butyrate secretion is challenging.
• Coculturing acetogens with other bacteria offers an alternative for efficient butyrate production from CO.
• Exploiting native microbial capabilities can overcome limitations of metabolic engineering.

Purpose of the Study:

• To computationally evaluate coculture systems for converting CO to butyrate.
• To identify suitable gut bacteria for acetate-to-butyrate conversion.
• To guide experimental design for novel microbial production systems.

Main Methods:

• Dynamic metabolic modeling and flux balance analysis were employed.
• A screening procedure identified gut bacteria meeting growth and conversion criteria.
• 170 acetogen/gut bacterium/sugar combinations were simulated under continuous CO/CO2 gas mixture.

Main Results:

• Cocultures with Eubacterium limosum or Blautia producta showed low butyrate productivity.
• Clostridium ljungdahlii and C. autoethanogenum were identified as promising CO-to-acetate converters.
• Pairings with Clostridium hylemonae or Roseburia hominis demonstrated high butyrate productivity.

Conclusions:

• Metabolic modeling provides valuable insights for coculture design.
• Promising coculture designs were predicted, suitable for experimental realization.
• Specific acetate secretion rate of C. ljungdahlii was more beneficial than C. autoethanogenum's growth rate for butyrate productivity.