Search bioRxiv⌕ Search

Biology subjects

Toepfer, N.

Publications and source records attributed to Toepfer, N..

3 recordsLinked to original sources

Accessing Enzyme Kinetic Data and Prediction Methods at Scale

Enzyme kinetic parameters inform metabolic models, yet experimental measurements are sparse. A growing body of work predicts them from protein and substrate features, but software fragmentation hinders adoption, so downstream tools lock into the most accessible method. We present OpenKinetics Predictor (at predictor.openkinetics.org), an open-source platform integrating thirteen methods in isolated environments behind one interface. The platform optionally reports similarity between query proteins and each method's training data to contextualise reliability. A common featurisation-prediction abstraction keeps it extensible, and independent parties, including original authors, contributed many methods. We pair it with a data portal (at data.openkinetics.org) that exposes CatLog, a curated kinetic dataset, with precomputed embeddings, predicted binding sites, and standardised splits. Both offer a web interface and an API, and the GECKO modelling toolbox already calls the predictor API. As a case study, we predict across an E. coli model and find inter-predictor agreement varies with metabolic context and data availability.

systems biology↗

Metabolic profiling and genome-scale modelling uncover mechanistic drivers of microbiome stability in synthetic maize root community

Stability is a desirable property for agricultural microbiomes, but there is a poor understanding of the mechanisms that mediate microbial community stability. A representative bacterial synthetic community from maize roots has been proposed by Niu et al. (2017, PNAS, 114:E2450) as a model system to study microbiome stability. This SynCom assembles stably when all seven members are present, but community diversity collapses without the keystone E. ludwigii strain. In this study, we used complementary in vitro experiments and in silico metabolic modelling to assess the role of metabolites for the stability of this SynCom, by defining the metabolic niches occupied by each strain, as well as their cross-feeding phenotypes and B-vitamin dependencies. We show that the individual member strains occupy complementary metabolic niches, measured by the depletion of distinct metabolites in exometabolomic experiments, as well as contrasting growth phenotypes on diverse carbon substrates, patterns which are largely recapitulated by computational simulations. Minimal medium experiments show that the established seven-member community comprises a mixture of prototrophic and auxotrophic strains. Correspondingly, experimental and in silico cross-feeding phenotypes showed that spent media harvested from the prototrophic strains can sustain growth of two auxotrophs and let to the identification of B-vitamin dependencies. Altogether, this study highlights the complementary power of in vitro and in silico approaches and suggests that the metabolic mechanisms of this SynCom can serve as design principles to inform the rational assembly of stable plant-associated microbial communities.

microbiology↗

CAM emerges in a leaf metabolic model under water-saving constraints in different environments

Crassulacean Acid Metabolism (CAM) evolved in arid environments as a water-saving alternative to C3 photosynthesis. There is great interest in engineering more drought-resistant crop species by introducing CAM into C3 plants. However, one of the open questions is whether full CAM or alternative water-saving flux modes would be more productive in the environments typically experienced by C3 crops. To study the effect of temperature and relative humidity on plant metabolism we coupled a time-resolved diel model of leaf metabolism to an environment-dependent gas-exchange model. This model allowed us to study the emergence of CAM or CAM-like behaviour as a result of a trade-off between leaf productivity and water-saving. We show that vacuolar storage capacity in the leaf is a major determinant of the extent of CAM and shapes the occurrence of phase II and IV of the CAM cycle. Moreover, the model allows us to study alternative flux routes and we identify mitochondrial isocitrate dehydrogenase (ICDH) and an isocitrate-citrate-proline-2OG cycle as a potential contributor to initial carbon fixation at night. Simulations across a wide range of environmental parameters show that the water-saving potential of CAM strongly depends on the environment and that the additional water-saving effect of carbon fixation by ICDH can reach up to 4% for the conditions tested.

plant biology↗