title: Functional metabolic map of Faecalibacterium prausnitzii, a beneficial human gut microbe.
abstract: The human gut microbiota plays a central role in human well-being and disease. In this study, we present an integrated, iterative approach of computational modeling, in vitro experiments, metabolomics, and genomic analysis to accelerate the identification of metabolic capabilities for poorly characterized (anaerobic) microorganisms. We demonstrate this approach for the beneficial human gut microbe Faecalibacterium prausnitzii strain A2-165. We generated an automated draft reconstruction, which we curated against the limited biochemical data. This reconstruction modeling was used to develop in silico and in vitro a chemically defined medium (CDM), which was validated experimentally. Subsequent metabolomic analysis of the spent medium for growth on CDM was performed. We refined our metabolic reconstruction according to in vitro observed metabolite consumption and secretion and propose improvements to the current genome annotation of F. prausnitzii A2-165. We then used the reconstruction to systematically characterize its metabolic properties. Novel carbon source utilization capabilities and inabilities were predicted based on metabolic modeling and validated experimentally. This study resulted in a functional metabolic map of F. prausnitzii, which is available for further applications. The presented workflow can be readily extended to other poorly characterized and uncharacterized organisms to yield novel biochemical insights about the target organism.
authors.affiliation: Luxembourg Center for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors.forename: Almut
authors.initials: A
authors.lastname: Heinken
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: M Tanweer
authors.initials: MT
authors.lastname: Khan
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paglia
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California, USA A. A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Rodionov
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hermie J M
authors.initials: HJ
authors.lastname: Harmsen
authors.affiliation: Luxembourg Center for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg Center for Systems Biology, University of Iceland, Reykjavik, Iceland ines.thiele@uni.lu.
authors.forename: Ines
authors.initials: I
authors.lastname: Thiele
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016208:Databases, Factual; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D016680:Genome, Bacterial; D006094:Gram-Positive Bacteria / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D001426:Bacterial Proteins