Abstract
BackgroundSaccharopolyspora erythraea (S. erythraea) is a Gram-positive erythromycin–producing filamentous bacterium. The lack of comprehensive S. erythraea genome-scale metabolic models (GEMs) hinders the efficiency of metabolic engineering as well as fermentation process optimization.ResultsIn this study, the GEMs model of S. erythraea iZZ1342 was reconstructed according to the latest genome annotations, omics databases, and literatures. Compared with the previous S. erythraea model—GSMR, the new model iZZ1342 presented great improvements both on scope and coverage in the number of reactions, metabolites, and annotated genes. In detail, the number of unique reactions in iZZ1342 was increased from 1482 to 1684, the number of metabolites was increased from 1546 to 1614, and the number of unique genes was increased from 1272 to 1342. We also added 1441 gene-protein-reaction associations in iZZ1342 which lacks in the previous model to overcome the limitation in the application of strain designing. Compared with the transcriptomics data obtained from the published literature, 86.3% ORFs and 92.9% reactions in iZZ1342 can be verified. The results of the sensitivity analysis showed the similar trend in the E. coli GEMs. The prediction of growth on available 27 kinds of carbon sources and 33 kinds of nitrogen sources showed the accuracy rate was 77.8 and 87.9%, respectively. Compared with the physiological data obtained from chemostat cultivation, the simulation results showed good consistency. The correlation coefficient between the 13C-labeled experiment data and the flux simulation result was 0.97. All the above results showed that the iZZ1342 model has good performance. Furthermore, four genes are in the range of successful knockout by comparing these targets with the results which have been earlier published.ConclusionThe new model iZZ1342 improved significantly in model size and prediction performance, which will lay a good foundation to study the systematic metabolic engineering of S. erythraea system in vivo.
Highlights
Saccharopolyspora erythraea (S. erythraea) is a Gram-positive erythromycin–producing filamentous bacterium
Abstract genome data and intracellular metabolic pathways are transformed into mathematical models, which make systems biology developed tremendously (Ellis and Goodacre 2012)
With the development of modern genome sequencing, it is possible to integrate the reconstruction of metabolic pathways into Genome-Scale Metabolic Model (GEM)
Summary
Saccharopolyspora erythraea (S. erythraea) is a Gram-positive erythromycin–producing filamentous bacterium. Saccharopolyspora erythraea, formerly called Streptomyces erythraeus (Weber et al 1985), is a kind of Gram-positive filamentous bacterium which produces the medically useful antibiotic erythromycin A (Oliynyk et al 2007). Systems biology is a kind of discipline which combines experimental and computational methods (Feist and Al 2009) This method is useful to make a comprehensive analysis and prediction of complex intracellular biological systems. Abstract genome data and intracellular metabolic pathways are transformed into mathematical models, which make systems biology developed tremendously (Ellis and Goodacre 2012). The Genome-Scale Metabolic Models (GEMs) are becoming one of the most significant tools for analyzing different metabolites and metabolic pathways in metabolic engineering (Kim et al 2012). With the development of modern genome sequencing, it is possible to integrate the reconstruction of metabolic pathways into GEMs
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