Reconstruction and Quality Control of a Genome-Scale Metabolic Model for Methylococcus capsulatus

Christian Lieven

Research output: Book/ReportPh.D. thesis

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Climate-change induced food scarcity is a grim prospect for the future of humanity. Alas, increasingly detrimental effects of global warming and overpopulation are predicted to beget this outlook by the year 2050. Fortunately, the production of single-cell protein (SCP) from microbial fermentations presents an answer since it circumvents having to expand a spatially limited agriculture. It represents a controllable, scalable approach to food production that can be developed on a number of industrial waste products. The greenhouse gas methane is released abundantly into the atmosphere by both agricultural and industrial processes. To capitalize on this resource, the
establishment of the protein-rich obligate methanotroph Methylcococcus capsulatus as an SCP product has been pursued. In addition, other methanotrophic organisms
have been considered as cell factories for the production of chemicals from methane. In this thesis, we recount the interplay between methane and the environment and outline the process of a genome-scale metabolic model (GEM) reconstruction. We then illuminate methods from software development that could streamline and quality control the reconstruction process, after which we continue to introduce existing genome-scale metabolic models of methanotrophs and their applications in biotechnology.
The main merit of this work lies in presenting memote (metabolic model tests), a set of community-curated test cases and the corresponding software, which enable
the automated quality control of GEMs independent from reconstruction platforms or analyses software. Memote strongly supports publicly hosted and
version controlled models, which we hope facilitates cross-communitycollaboration and research transparency. Furthermore, we present the first manually curated GEM of Methylococcus capsulatus. The model comprises 750 genes, 877 metabolites and 898 reactions and VI has been used to investigate the mode of electron transfer in this organism. Since it combines multi-layered biochemical and genomic information into one single knowledgebase, the availability of a GEM for M. capsulatus is an invaluable
prerequisite for rational strain engineering towards an improved SCP production.
Original languageEnglish
Place of PublicationKgs. Lyngby
PublisherTechnical University of Denmark
Number of pages151
Publication statusPublished - 2018


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