Pohlkotte, F. | bioRxiv Science

bioRxiv2026

Steady state ratios in bipartite population models emerge through obligate cross-feeding

Cross-feeding, the phenomenon where one organism consumes metabolites secreted by another, is a ubiquitious phenomenon in microbial communities. Obligate, mutually cross-feeding organisms are a special case of mutualism, where each organism produces a resource that the other organism requires for growth. Many obligate, mutually cross-feeding microbial systems have been studied, including naturally occurring as well as synthetically designed communities. Interestingly, in all these experimental systems it has been observed that the communities approach a fixed biomass ratio, independent of the initial biomass inoculation composition. The repeated reports of stable biomass ratios suggest that such ratios are actually a generic property of mutually obligate cross-feeding systems and that, if the system is stable, such a ratio must be approached. As a consequence, it should also be possible to explain and predict this ratio from measurable parameters. Here, we explore mutually obligate cross-feeding systems with mathematical models and show that a stable biomass ratio is a general feature of such systems. Moreover, we show how this ratio can be predicted from key parameters that can be interpreted as the value of the resource to the consuming organism and the cost of producing a resource to the producing organism.

systems biology↗

bioRxiv2023

Microbial pathway thermodynamics: structural models unveil anabolic and catabolic processes

The biotechnological exploitation of microorganisms enables the use of metabolism for the production of economically valuable substances, such as drugs or food. It is, thus, unsurprising that the investigation of microbial metabolism and its regulation has been an active research field for many decades. As a result, several theories and techniques were developed that allow the prediction of metabolic fluxes and yields as biotechnologically relevant output parameters. One important approach is to derive macrochemical equations that describe the overall metabolic conversion of an organism and basically treat microbial metabolism as a black box. The opposite approach is to include all known metabolic reactions of an organism to assemble a genomescale metabolic model. Interestingly, both approaches are rather successful to characterise and predict the expected product yield. Over the years, especially macrochemical equations have been extensively characterised in terms of their thermodynamic properties. However, a common challenge when characterising microbial metabolism by a single equation is to split this equation into two, describing the two modes of metabolism, anabolism and catabolism. Here, we present strategies to systematically identify separate equations for anabolism and catabolism. Based on metabolic models, we systematically identify all theoretically possible catabolic routes and determine their thermodynamic efficiency. We then show how anabolic routes can be derived, and use these to approximate biomass yield. Finally, we challenge the view of metabolism as a linear energy converter, in which the free energy gradient of catabolism drives the anabolic reactions.

systems biology↗