Abstract
Corynebacterium glutamicum belongs to the microbes of enormous biotechnological relevance. In particular, its strain ATCC 13032 is a widely used producer of L-amino acids at an industrial scale. Its apparent robustness also turns it into a favorable platform host for a wide range of further compounds, mainly because of emerging bio-based economies. A deep understanding of the biochemical processes in C. glutamicum is essential for a sustainable enhancement of the microbe's productivity. Computational systems biology has the potential to provide a valuable basis for driving metabolic engineering and biotechnological advances, such as increased yields of healthy producer strains based on genome-scale metabolic models (GEMs). Advanced reconstruction pipelines are now available that facilitate the reconstruction of GEMs and support their manual curation. This article presents iCGB21FR, an updated and unified GEM of C. glutamicum ATCC 13032 with high quality regarding comprehensiveness and data standards, built with the latest modeling techniques and advanced reconstruction pipelines. It comprises 1042 metabolites, 1539 reactions, and 805 genes with detailed annotations and database cross-references. The model validation took place using different media and resulted in realistic growth rate predictions under aerobic and anaerobic conditions. The new GEM produces all canonical amino acids, and its phenotypic predictions are consistent with laboratory data. The in silico model proved fruitful in adding knowledge to the metabolism of C. glutamicum: iCGB21FR still produces L-glutamate with the knock-out of the enzyme pyruvate carboxylase, despite the common belief to be relevant for the amino acid's production. We conclude that integrating high standards into the reconstruction of GEMs facilitates replicating validated knowledge, closing knowledge gaps, and making it a useful basis for metabolic engineering. The model is freely available from BioModels Database under identifier MODEL2102050001.
Highlights
The strain Corynebacterium glutamicum ATCC 13032 is a Gram-positive, facultatively anaerobic soil bacterium, which produces L-glutamate under particular treatments or growth conditions (Kimura, 2005)
We present an updated genome-scale metabolic models (GEMs) of high quality for C. glutamicum named iCGB21FR
Strain The GEM of the strain Corynebacterium glutamicum ATCC 13032 was reconstructed using the annotated genome sequence, which was downloaded from the National Center for Biotechnology Information (NCBI) at https://www.ncbi.nlm.nih.gov (Agarwala et al, 2018)
Summary
The strain Corynebacterium glutamicum ATCC 13032 is a Gram-positive, facultatively anaerobic soil bacterium, which produces L-glutamate under particular treatments or growth conditions (Kimura, 2005). Despite an ongoing biotechnological application of C. glutamicum and the resulting knowledge on this bacterium for more than 70 years (Vertes et al, 2013), its metabolic potential not yet exhausted. One method of formalizing this knowledge is a genomescale metabolic network reconstruction. Genome-scale metabolic network reconstructions represent a systematic knowledge base of bibliomic and genomic data of all known metabolic reactions of a specific target organism (Thiele and Palsson, 2010). By creating a mathematical representation of the reconstructed network, the network can be changed into a genome-scale metabolic model (GEM). GEMs enable the qualitative description of the genotype-phenotype relationship and predictions of various phenotypes (Fang et al, 2020)
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