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

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.