Abstract
BackgroundActinobacillus succinogenes is a promising bacterial catalyst for the bioproduction of succinic acid from low-cost raw materials. In this work, a genome-scale metabolic model was reconstructed and used to assess the metabolic capabilities of this microorganism under producing conditions.ResultsThe model, iBP722, was reconstructed based on the functional reannotation of the complete genome sequence of A. succinogenes 130Z and manual inspection of metabolic pathways, covering 1072 enzymatic reactions associated with 722 metabolic genes that involve 713 metabolites. The highly curated model was effective in capturing the growth of A. succinogenes on various carbon sources, as well as the SA production under various growth conditions with fair agreement between experimental and predicted data. Calculated flux distributions under different conditions show that a number of metabolic pathways are affected by the activity of some metabolic enzymes at key nodes in metabolism, including the transport mechanism of carbon sources and the ability to fix carbon dioxide.ConclusionsThe established genome-scale metabolic model can be used for model-driven strain design and medium alteration to improve succinic acid yields.
Highlights
Actinobacillus succinogenes is a promising bacterial catalyst for the bioproduction of succinic acid from low-cost raw materials
A. succinogenes genome-scale metabolic network The construction of the Genome-scale metabolic models (GSMMs) for A. succinogenes 130Z was carried out in three different phases: (1) first, metabolic functions were assigned to genes; (2) biochemical reactions and enzymatic complexes were compiled to build a draft metabolic model, (3) which was thereafter completed and corrected by defining a biomass reaction, identifying network gaps and correcting inconsistencies when comparing with reported information
The model is available as a Systems Biology Markup Language (SBML) file at http://darwin.di.uminho.pt/models and BioModels database [61] assigned with the identifier MODEL1804130001 and detailed information on the curated metabolic network can be found in Additional file 2
Summary
Actinobacillus succinogenes is a promising bacterial catalyst for the bioproduction of succinic acid from low-cost raw materials. Actinobacillus succinogenes is a gram-negative facultative anaerobic bacterium and is one of the major natural producers of succinic acid (SA). It can grow on a broad range of substrates, including arabinose, cellobiose, fructose, galactose, glucose, lactose, maltose, mannitol, mannose, sucrose and xylose, producing a mixture of by-products (e.g., SA, formic acid (FA), acetic acid (AA), and ethanol (EtOH)) as the main by-products [1, 2]. Its tolerance to high sugar concentrations (up to 160 g.L− 1 of glucose [3]) and high levels of organic acids [4], as well as its capnophilic nature [5], make this microorganism potentially interesting for the production of SA at the industrial scale. High-titer succinate production using low-cost feedstocks like cane molasses or corn straw has been obtained [2, 6,7,8,9,10,11,12,13,14,15]; significant
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