Genome-scale metabolic modeling of Ruminiclostridium cellulolyticum: a microbial cell factory for valorization of lignocellulosic biomass.

The development of sustainable biotechnological processes requires a transition from the traditional fermentation of refined substrates toward the valorization of waste materials such as lignocellulosic biomass. Although these so-called recalcitrant substrates cannot be degraded by model industrial organisms, they can be degraded by microbial consortia through a process of anaerobic digestion, where different community members are able to break down polysaccharides of varied complexity. Among these microbes, Ruminiclostridium cellulolyticum stands out as a promising candidate for fermentation of lignocellulose due to its ability to degrade both cellulose and hemicellulose. In this work, we present an updated genome-scale metabolic model for R. cellulolyticum strain H10. The model was manually curated with experimental data, and the pathways for degradation of cellulose and hemicellulose (arabinoxylan and xyloglucan) were reconstructed and annotated with full detail. The model enables the simulation of the fermentation profile of lignocellulosic materials of various compositions, facilitating the use of this organism as a potential workhorse for sustainable biotechnology, and it provides a valuable template for the reconstruction and optimization of lignocellulose degradation pathways in related organisms.

Importance: In this work, we present a manually curated genome-scale metabolic model for Ruminiclostridium cellulolyticum, one of the few species known to fully degrade cellulose and hemicellulose. The model was extensively curated with experimental data obtained from the literature, covering approximately 25 years of research on this organism. We use this model to simulate the fermentation of mixed lignocellulosic polysaccharides and observe a good agreement with experimental data. This organism is therefore a promising microbial cell factory for sustainable transformation of lignocellulosic residues into valuable industrial products.