(614d) Engineering a Syntrophic Clostridium Consortium Enabling Mixotrophic Biochemical Production with CO2 Fixation and Transformative Product Yields

The dual challenge for chemical manufacturers is to meet ever-growing demands while reducing greenhouse gas emission. Developing a carbon neutral or negative microbial chemical production platform is a compelling approach for sustainable bioeconomy. A critical question for affordable microbial chemical production is how to achieve high production yield. For example, sugar catabolism leads to loss of a third of carbon as CO₂, decreasing theoretical maximum product yields. To address the question, we vouch for mixotrophy, whereby sugar substrates are consumed together with electron-rich sources (e.g., H₂) and CO₂. Synthetic syntrophy is a promising strategy to harness modularity of microbial consortia for mixotrophic biochemical production at industrially relevant scale. Syntrophy is obligately mutualistic metabolism stabilizing coculture population. In this talk, we will discuss how to enable mixotrophic isopropanol production by engineering a syntrophic Clostridium consortium consisting of C. acetobutylicum (Cac) and C. ljungdahlii (Clj). Understanding interactions between the two species is important to achieve supra-theoretical product yields. We will address three questions: 1) how do the two different Clostridium communicate with each other; 2) how does the metabolism of individual strains affect each other; and 3) how can we engineer the syntrophic consortium to minimize carbon loss and maximize product yields. We will present synthetic biology and metabolic engineering strategies to demonstrate that reassimilating the CO₂ into isopropanol production pathway not only reduces CO₂ emission from sugar fermentation, but also enables selective isopropanol production at transformative yields. The concept is generalizable for other biochemical, biomaterial, and biofuel production.