CBE Seminar: Eleftherios T. Papoutsakis

Title: Production of Chemicals from Mixotrophic Clostridium Cocultures Enabling CO₂ Fixation to Achieve Transformative Product Yields

Abstract
Developing a carbon neutral or negative chemical production platform is a compelling approach to establish a sustainable bio-based economy. I will discuss synthetic Clostridium acetobutylicum and C. ljungdalhii consortia that enable biological production of metabolites at supra-theoretical yields from sugar catabolism. Through heterogenous cell fusion, Clostridium strains efficiently exchange cellular materials, enabling supra-theoretical yields for metabolite production from sugar fermentation. We engineered C. acetobutylicum in order to increase product selectivity focusing on isopropanol (IPA) production. The engineered strains were paired with C. ljungdalhii, which consumes CO₂ and H₂ and converts acetone to IPA using endogenous dehydrogenases. The goal is to produce IPA with minimal carbon loss and in fact using exogenously supplied CO₂ and electrons. Our strategy involves both strain engineering and bioreactor operation strategies working synergistically to achieve targeted performance metrics. IPA serves as biofuel component or a valuable chemical with a Market Size of $2.65B (2019) & a CAGR of 8.2% (2020-27). The concept can be extended to the production of several native and non-native metabolites by engineering one or both partners. Significantly, several more coculture pairs can be explored to diversify the metabolite space. These engineered syntrophic Clostridium consortia represent a promising platform for carbon neutral or negative production of chemicals and fuels.

Bio

Eleftherios (Terry) Papoutsakis is the Unidel Eugene DuPont Professor at the Department of Chemistry & Biomolecular Engineering at the University of Delaware. Papoutsakis has made important contributions in both microbial and animal-cell biotechnology. Microbial biotechnology work includes contributions in clostridia genetics and metabolic engineering with emphasis recently in syntrophic co-cultures for CO₂ co-utilization with biomass carbohydrates to achieve supra-physiological product yields, but also E. coli biotechnology including synthetic methylotrophy and stress tolerance. Animal-cell biotechnology includes seminal work on mixing and agitation in cell-culture bioreactors, and stem-cell bioengineering and the use of extracellular vesicles for applications in cell and gene therapies.

Papoutsakis has been recognized by numerous awards, including election to National Academy of Engineering (NAE), National Academy of Inventors (NAI) & International Academy of Medical & Biological Engineering (IAMBE), the 2020 American Society for Microbiology (ASM) National Award in Applied Biotechnology, the 2017 Amer. Chemical Society (ACS) E. V. Murphree Award in Industrial & Engineering Chemistry, the 2013 DIC Wang for Excellence in Biochemical Engineering (SBE/AIChE), the 2012 James E. Bailey Award (SBE/AIChE); election as ACS Fellow, the 2010 Metabolic Engineering Award, the 2005 Amgen Biochemical Engineering Award, the 2004 Merck Cell Culture Engineering Award & the 2003 Alpha Chi Sigma AIChE Award. He received his BS from the National Technical University of Athens & his MS/PhD from Purdue University. He has supervised over 70 PhD, 30 MS, 35 postdoctoral and 80 undergraduate research students, funded by over $50 million in grants from NSF, NIH, DOE, ARPA-E, ONR & ARO.