Modeling a co-culture of Clostridium autoethanogenum and Clostridium kluyveri to increase syngas conversion to medium-chain fatty-acids

Microbial fermentation of synthesis gas (syngas) is becoming more attractive for sustainable production of commodity chemicals. To date, syngas fermentation focuses mainly on the use of Clostridium species for the production of small organic molecules such as ethanol and acetate. The co-cultivation of syngas-fermenting microorganisms with chain-elongating bacteria can expand the range of possible products, allowing, for instance, the production of medium-chain fatty acids (MCFA) and alcohols from syngas. To explore these possibilities, we report herein a genome-scale, constraint-based metabolic model to describe growth of a co-culture of Clostridium autoethanogenum and Clostridium kluyveri on syngas for the production of valuable compounds. Community flux balance analysis was used to gain insight into the metabolism of the two strains and their interactions, and to reveal potential strategies enabling production of butyrate and hexanoate. The model suggests that addition of succinate is one strategy to optimize the production of medium-chain fatty-acids from syngas with this co-culture. According to the predictions, addition of succinate increases the pool of crotonyl-CoA and the ethanol/acetate uptake ratio in C. kluyveri, resulting in the flux of up to 60% of electrons into hexanoate. Other potential way to optimize butyrate and hexanoate is to increase ethanol production by C. autoethanogenum. Deletion of either formate transport, acetaldehyde dehydrogenase or formate dehydrogenase (ferredoxin) from the metabolic model of C. autoethanogenum leads to a (potential) increase in ethanol production up to 150%, which is clearly very attractive.