RT Journal Article T1 Steerable isobutyric and butyric acid production from CO2 and H2 by Clostridium luticellarii A1 Quinten, Mariën A1 Regueira López, Alberte A1 Ganigué, Ramon AB Clostridium luticellarii is a recently discovered acetogen that is uniquely capable of producing butyric and isobutyric acid from various substrates (e.g. methanol), but it is unclear which factors influence its (iso)butyric acid production from H2 and CO2. We aimed to investigate the autotrophic metabolism of C. luticellarii by identifying the necessary growth conditions and examining the effects of pH and metabolite levels on product titers and selectivity. Results show that autotrophic growth of C. luticellarii requires the addition of complex nutrient sources and the absence of shaking conditions. Further experiments combined with thermodynamic calculations identified pH as a key parameter governing the direction of metabolic fluxes. At circumneutral pH (~6.5), acetic acid is the sole metabolic end product but C. luticellarii possesses the unique ability to co-oxidize organic acids such as valeric acid under high H2 partial pressures (>1 bar). Conversely, mildly acidic pH (≤5.5) stimulates the production of butyric and isobutyric acid while partly halting the oxidation of organic acids. Additionally, elevated acetic acid concentrations stimulated butyric and isobutyric acid production up to a combined selectivity of 53 ± 3%. Finally, our results suggest that isobutyric acid is produced by a reversible isomerization of butyric acid, but valeric and caproic acid are not isomerized. These combined insights can inform future efforts to optimize and scale-up the production of valuable chemicals from CO2 using C. luticellarii PB Wiley SN 1751-7915 YR 2023 FD 2023 LK http://hdl.handle.net/10347/30966 UL http://hdl.handle.net/10347/30966 LA eng NO Mariën, Q., Regueira, A. & Ganigué, R. (2023) Steerable isobutyric and butyric acid production from CO2 and H2 by Clostridium luticellarii. Microbial Biotechnology, 00, 1–16. Available from: https://doi.org/10.1111/1751-7915.14321 NO Galician Competitive Research Group. Grant Numbers: ERDF (UE), GRC ED431C 2021/37. Bijzonder Onderzoeksfonds UGent. Grant Number: BOF19/STA/044. Fonds Wetenschappelijk Onderzoek. Grant Number: 1SC5722N. Xunta de Galicia. Grant Number: ED481B-2021-012 DS Minerva RD 25 abr 2026