N. Mushnikov
AsimicA, Inc,
United States
Keywords: bio-manufacturing, bioeconomy, synthetic biology, fermentation, biofuel, sustainability
Summary:
Bio-manufacturing is one of the key objectives for a sustainable future economy. Genetically engineered microbes can produce all types of chemical molecules ranging from commodity chemicals to advanced therapeutics. Broad application of bio-based manufacturing is limited due to economic inefficiency caused by low productivity. Highest-yielding microbial strains are destined to sacrifice their energy and metabolites for biosynthesis. A common solution is to separate the active production phase from biomass generation. Thus, productivity is sequestered for a relatively short time at the end of the cycle, while a longer biomass-generating phase contributes to high OpEx. Our innovation of Microbial Stem Cells is a way to combine active production and culture regeneration. The principle is to enable different roles for subpopulations producing Factory cells and regenerative Stem cells within isogenic culture. In our trials, we programmed E. coli Factory cells to yield a high level of target protein biosynthesis (e.g., Insulin). Stem-cell-mediated regeneration helped to triplicate productivity, compared to conventional uniform cultures. Currently, we are working on the NSF SBIR-funded project to demonstrate a similar effect on the efficiency of terpenoid production in E. coli. The biosynthetic pathway is known to be toxic for producing cells, suggesting that regeneration abilities in producing culture would have a particularly high impact on the process efficiency. We aim to demonstrate the potential of Microbial Stem Cell Technology to improve various fermentation processes. The industrial application of our approach would contribute to a sufficient decrease in OpEx of bio-manufacturing to improve economic efficiency.