Implementation of a Clostridium luticellarii genome-scale model for upgrading syngas fermentations

Syngas fermentation is a powerful platform for converting waste streams into sustainable carboxylic acid precursors for value-added biochemicals. Steel mills produce significant syngas, yet industrial microbial syngas valorization remains unrealized. The most promising syngas-converting biocat-alysts consist of Clostridia species, such as Clostridium kluyveri, Clostridium autoethanogenum, and Clostridium ljungdahlii. Clostridium luticellarii, a recently discovered species, shares close phylogenetic ties with these organisms. Preliminary metabolic studies suggest its potential for syngas acetogenesis as well as chain elongation. In this study, we create iSJ444, a constraint-based metabolic model of C. luticellarii using iHN637 of a close relative C. ljungdahlii as a starting point. Model predictions support hypothesized methanol and syngas pathways from the metabolic characterization studies; however, the use of propionate could not be accurately predicted. Thermodynamic Flux Analysis (TFA) reveals that C. luticellarii maintains stable energy dissipation across most reactions when exposed to varying pH, with significant increases observed in reactions associated with the Wood-Ljungdahl pathway (WLP), such as the HACD1 reaction, at higher pH (6.5), suggesting an adaptive role in energy management under neutral conditions. Flux sampling simulations exploring metabolic flux distributions show that C. luticellarii might fit into syngas fermenting platforms. In both cases, high hydrogen-to-carbon source ratios result in better production of (iso)butyrate and caproate. We present a minimal genome-scale metabolic model of C. luticellarii as a foundation for further exploration and optimization. Although our predictions of its metabolic behavior await experimental validation, they underscore the potential of C. luticellarii to enhance syngas fermentation platforms. HighlightsO_LIiSJ444 models C. luticellarii metabolism for syngas fermentation and chain elongation. C_LIO_LIThermodynamic flux analysis (TFA) reveals adaptive energy balancing in pathways. C_LIO_LISimulations highlight C. luticellarii as a producer of value-added biochemicals like butyrate, isobutyrate, and caproate C_LIO_LIMetabolic insights from iSJ444 suggest efficient syngas conversion using varied substrates for industrial use. C_LI