Genome-scale metabolic models (GEMs) are valuable tools to study metabolism and provide a scaffold for the integrative analysis of omics data. Researchers have developed increasingly comprehensive human GEMs, but the disconnect among different model sources and versions impedes further progress. We therefore integrated and extensively curated the most recent human metabolic models to construct a consensus GEM, Human1. We demonstrated the versatility of Human1 through the generation and analysis of cell- and tissue-specific models using transcriptomic, proteomic, and kinetic data. We also present an accompanying web portal, Metabolic Atlas (https://www.metabolicatlas.org/), which facilitates further exploration and visualization of Human1 content. Human1 was created using a version-controlled, open-source model development framework to enable community-driven curation and refinement. This framework allows Human1 to be an evolving shared resource for future studies of human health and disease.

Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer’s disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.

BACKGROUND Design principles of a fed‐batch bioreactor system to fine‐tune bioreactor performance by increasing production and productivity are investigated. To enhance the production and productivity in fed‐batch fermentation of recombinant human growth hormone (rhGH) by Bacillus subtilis, this work develops a continuous feed stream (CFS) design method with the parameters, cultivation time to switch batch‐ to fed‐batch operation, so called transition time, tT, and specific growth rate, μ. RESULTS Based on batch‐bioreactor data for rhGH production by recombinant B. subtilis (scoC−) carrying pMK4::pre(subC)::hGH, three components of the defined medium were determined for continuous feeding. Theoretical analysis and modelling of the fed‐batch reactor lead to CFS design, to be applied starting at tT, which is a function of specific growth rate, μ. Transition time tT was optimised experimentally using the batch operation μ value, 0.100 h−1; and the highest rhGH concentration was obtained at tT=4 h. rhGH concentration increased further to 127 mg dm−3, when the CFS flow rate applied was calculated using μ = 0.125 h−1. CONCLUSION The performance of the fermentation process was enhanced by 36% and 8 h shortened cultivation time of t = 16 h, increased the rhGH productivity 2.4‐fold compared with batch‐fermentation. © 2015 Society of Chemical Industry

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This review focuses on the construction of a global, comprehensive understanding of Bacillus subtilis through microarray studies. The microarray studies in B. subtilis were analysed based on the theme of the work, by mentioning the growth media, bioreactor operation conditions, RNA isolation method, number of data points analysed in exponential or stationary phases, compared genotypes, induction and repression ratios, investigated gene(s) and their positive and/or negative influences. Based on the theme and scope of the studies, the articles were reviewed under seven thematic sections, i.e., effects of gene deletion(s) or overexpression, effects of overexression of heterologous genes, comparison of global gene expression between aerobic and anaerobic respiration, effects of temperature change, effects of transported molecules, effects of limitations and stress conditions, and other microarray studies in B. subtilis.

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