Genome-scale metabolic models consistently predict in vitro characteristics of Corynebacterium striatum

Front Bioinform. 2023 Oct 23:3:1214074. doi: 10.3389/fbinf.2023.1214074. eCollection 2023.

Abstract

Introduction: Genome-scale metabolic models (GEMs) are organism-specific knowledge bases which can be used to unravel pathogenicity or improve production of specific metabolites in biotechnology applications. However, the validity of predictions for bacterial proliferation in in vitro settings is hardly investigated. Methods: The present work combines in silico and in vitro approaches to create and curate strain-specific genome-scale metabolic models of Corynebacterium striatum. Results: We introduce five newly created strain-specific genome-scale metabolic models (GEMs) of high quality, satisfying all contemporary standards and requirements. All these models have been benchmarked using the community standard test suite Metabolic Model Testing (MEMOTE) and were validated by laboratory experiments. For the curation of those models, the software infrastructure refineGEMs was developed to work on these models in parallel and to comply with the quality standards for GEMs. The model predictions were confirmed by experimental data and a new comparison metric based on the doubling time was developed to quantify bacterial growth. Discussion: Future modeling projects can rely on the proposed software, which is independent of specific environmental conditions. The validation approach based on the growth rate calculation is now accessible and closely aligned with biological questions. The curated models are freely available via BioModels and a GitHub repository and can be used. The open-source software refineGEMs is available from https://github.com/draeger-lab/refinegems.

Keywords: Corynebacterium striatum; genome-scale metabolic models; model-driven discovery; opportunistic pathogen; software engineering; strain-specific model.

Grants and funding

This research was funded by the German Center for Infection Research (DZIF, doi: 10.13039/100009139) within the Deutsche Zentren der Gesundheitsforschung (BMBF-DZG, German Centers for Health Research of the Federal Ministery of Education and Research), grant [№ = 1] 8020708703 and supported by infrastructural funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Cluster of Excellence EXC 2124—390838134 Controlling Microbes to Fight Infections. The authors acknowledge support from the Open Access Publishing Fund of the University of Tübingen (https://uni-tuebingen.de/de/216529).