Abel, A.-S. | Search bioRxiv

bioRxiv2025

Computational Approaches in Chemical Space Exploration for Carbon Fixation Pathways

Chemical space exploration is an important part of chemistry and biology, enabling the discovery and optimization of metabolic pathways, advancing synthetic metabolic functions, and understanding biochemical network evolution. We use a graph-based computational approach implemented in the cheminformatics software MOD, integrated with Integer Linear Programming (ILP) optimization, to systematically search chemical spaces. This approach allows for flexible and targeted queries, including identification of autocatalytic cycles, thermodynamic considerations, and discovery of novel enzymatic cascades. Specifically, we explore the chemical space of natural and artificial carbon fixation pathways defined from relevant enzyme reactions. By applying different optimization criteria, we identify new varieties and recombinations of natural autocatalytic pathways, and compare the properties of the pathways. This work highlights the versatility of graph-based cheminformatics for the purpose of chemical space exploration and artificial pathway design. Potential applications of this framework extend to carbon capture technologies, improved agricultural yields, and value-added chemical production, advancing efforts to address global sustainability challenges.

systems biology↗

bioRxiv2023

Analysis of Metabolomics and Transcriptomics Data to Assess Interactions in Microalgal Co-culture of Skeletonema marinoi and Prymnesium parvum

In marine ecosystems, microbial communities often interact using specialised metabolites, which play a central role in shaping the dynamics of the ecological networks and maintaining the balance of the ecosystem. With metabolomics and transcriptomics analyses, this study explores the interactions between two marine microalgae, Skeletonema marinoi and Prymnesium parvum, grown in mono-cultures and non-contact co-cultures. As a growth indicator, the photosynthetic potential, measured via fluorescence, suggested chemical interaction between S. marinoi and P. parvum. Using Liquid Chromatography-Mass Spectrometry (LC-MS) data, we identified 346 and 521 differentially produced features in the endo- and exometabolome of S. marinoi and P. parvum, respectively. Despite limited tandem mass spectrometry data (MS2) for these features, we structurally annotated 14 compounds, most of which were previously under-studied specialised metabolites. Differential gene expression analysis was then performed on the transcriptomes of the microalgae, which uncovered differentially expressed genes involved in energy metabolism and cellular repair for both species. These metabolic and transcriptomics changes depict the adaptation of both species in the co-culture. However, further data acquisition and investigation will be necessary to confirm the type of interaction and the underlying mechanisms. ImportanceMarine microalgae have great ecological importance and biochemical potential. Among these microbes are the diatom Skeletonema marinoi, known for its marine biogeochemical cycling, and the haptophyte Prymnesium parvum, which poses adverse environmental consequences. Given these opposing roles for the two cosmopolitan microalgae, we designed a study using untargeted metabolomics and transcriptomics to acquire a comprehensive snapshot of their interactions, grown as mono-cultures and co-cultures. The statistical analysis of the chlorophyll a fluorescence levels, and the metabolomics and transcriptomics dataset revealed metabolic communication occurring among the two species via specialised metabolites and activated cellular repair mechanisms. These findings reveal the complexity of the interactions within marine microbial ecosystems, offering a foundation for future research to understand and harness marine ecological systems.

microbiology↗