AUTHOR=Benito-Vaquerizo Sara , Nouse Niels , Schaap Peter J. , Hugenholtz Jeroen , Brul Stanley , López-Contreras Ana M. , Martins dos Santos Vitor A. P. , Suarez-Diez Maria TITLE=Model-driven approach for the production of butyrate from CO2/H2 by a novel co-culture of C. autoethanogenum and C. beijerinckii JOURNAL=Frontiers in Microbiology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1064013 DOI=10.3389/fmicb.2022.1064013 ISSN=1664-302X ABSTRACT=One-carbon (C1) compounds are promising feedstocks for sustainable production of commodity chemicals. CO2 is a particularly advantageous C1-feedstock since it is an unwanted industrial off-gas that can be converted to valuable products while reducing its atmospheric levels. Acetogens are known microorganisms that can grow on CO2/H2 and syngas converting these substrates into ethanol and acetate. Co-cultivation of acetogens with microbes that can further process such products can expand the variety of products to, for example, medium chain fatty acids (MCFA) and longer chain alcohols. Solventogens are microorganisms known to produce MCFA and alcohols via the acetone, butanol and ethanol (ABE) fermentation in which acetate is a key metabolite. Thus, co-cultivation of a solventogen and acetogen in a consortium provides a potential platform to produce valuable chemicals from CO2. In this study, metabolic modelling was implemented to design a new co-culture of an acetogen and a solventogen to produce butyrate from CO2/H2 mixtures. The model-driven approach suggested the ability of the studied solventogenic species to grow on lactate/glycerol with acetate as co-substrate. This ability was confirmed experimentally by cultivation of C. beijerinckii on these substrates in serum bottles and subsequently in pH-controlled bioreactors. Community modelling also suggested that a novel microbial consortium consisting of the acetogen Clostridium autoethanogenum, and the solventogen Clostridium beijerinckii would be feasible and stable. On the basis of this prediction, a co-culture was experimentally established. C. autoethanogenum grew on CO2/H2 producing acetate and traces of ethanol. Acetate was in turn, consumed by C. beijerinckii together with lactate, producing butyrate. These results show that community modelling of metabolism is a valuable tool to guide the design of microbial consortia for the tailored production of chemicals from renewable resources.