Development and experimental verification of a genome-scale metabolic model for Corynebacterium glutamicum

<p>Abstract</p> <p>Background</p> <p><it>In silico </it>genome-scale metabolic models enable the analysis of the characteristics of metabolic systems of organisms. In this study, we reconstructed a genome-scale metabolic model of <it>Corynebacterium glutamicum </it>on the basis of genome sequence annotation and physiological data. The metabolic characteristics were analyzed using flux balance analysis (FBA), and the results of FBA were validated using data from culture experiments performed at different oxygen uptake rates.</p> <p>Results</p> <p>The reconstructed genome-scale metabolic model of <it>C. glutamicum </it>contains 502 reactions and 423 metabolites. We collected the reactions and biomass components from the database and literatures, and made the model available for the flux balance analysis by filling gaps in the reaction networks and removing inadequate loop reactions. Using the framework of FBA and our genome-scale metabolic model, we first simulated the changes in the metabolic flux profiles that occur on changing the oxygen uptake rate. The predicted production yields of carbon dioxide and organic acids agreed well with the experimental data. The metabolic profiles of amino acid production phases were also investigated. A comprehensive gene deletion study was performed in which the effects of gene deletions on metabolic fluxes were simulated; this helped in the identification of several genes whose deletion resulted in an improvement in organic acid production.</p> <p>Conclusion</p> <p>The genome-scale metabolic model provides useful information for the evaluation of the metabolic capabilities and prediction of the metabolic characteristics of <it>C. glutamicum</it>. This can form a basis for the <it>in silico </it>design of <it>C. glutamicum </it>metabolic networks for improved bioproduction of desirable metabolites.</p

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既設鋼管鉄塔主柱材の耐風補強に関する研究 : 添接材工法の開発とその補強効果[松永]蓄熱式電気床暖房システムに関する研究[篠﨑]超々高層建築物の風応答予測のための高々度風観測手法および観測資料に利用に関する研究[林田]CFT造充填コンクリートの施工品質に関する研究[神代]高力ボルト摩擦すべりダンパーの履歴特性を応用した建築耐震構造に関する開発研究[吉岡]鋼・コンクリート合成構造の耐力と変形性能に関する研究[藤永]Memory and Continuity of Old Traditional House in Kotagede Area, Indonesia : through the analysis of psychological structure of the memory episode and its influence.[Pramitasari]市町村における都市計画マスタープランの策定と実施プロセスに関する研究[増田]子どもの「遊びの場」の構造に関する研究 : 通学路における道草遊びと道環境とのかかわりから[水月]水平・上下の入力地震動の相関性と構造物の組み合わせ応答の関係に関する研究[園]高品質コンクリートの硫酸酸性環境下における耐久性能に関する研究[原田]コンサートホール音場の空間印象評価に関する研究[和久田]Dry-masonry Brick House System as an \u22Adaptable Building\u22 Model for Asian Markets[Khamidi

THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer

Abstract Mesenchymal activation, characterized by dense stromal infiltration of immune and mesenchymal cells, fuels the aggressiveness of colorectal cancers (CRC), driving progression and metastasis. Targetable molecules in the tumor microenvironment (TME) need to be identified to improve the outcome in CRC patients with this aggressive phenotype. This study reports a positive link between high thrombospondin-1 (THBS1) expression and mesenchymal characteristics, immunosuppression, and unfavorable CRC prognosis. Bone marrow-derived monocyte-like cells recruited by CXCL12 are the primary source of THBS1, which contributes to the development of metastasis by inducing cytotoxic T-cell exhaustion and impairing vascularization. Furthermore, in orthotopically generated CRC models in male mice, THBS1 loss in the TME renders tumors partially sensitive to immune checkpoint inhibitors and anti-cancer drugs. Our study establishes THBS1 as a potential biomarker for identifying mesenchymal CRC and as a critical suppressor of antitumor immunity that contributes to the progression of this malignancy with a poor prognosis

学位論文審査報告

既設鋼管鉄塔主柱材の耐風補強に関する研究 : 添接材工法の開発とその補強効果[松永]蓄熱式電気床暖房システムに関する研究[篠﨑]超々高層建築物の風応答予測のための高々度風観測手法および観測資料に利用に関する研究[林田]CFT造充填コンクリートの施工品質に関する研究[神代]高力ボルト摩擦すべりダンパーの履歴特性を応用した建築耐震構造に関する開発研究[吉岡]鋼・コンクリート合成構造の耐力と変形性能に関する研究[藤永]Memory and Continuity of Old Traditional House in Kotagede Area, Indonesia : through the analysis of psychological structure of the memory episode and its influence.[Pramitasari]市町村における都市計画マスタープランの策定と実施プロセスに関する研究[増田]子どもの「遊びの場」の構造に関する研究 : 通学路における道草遊びと道環境とのかかわりから[水月]水平・上下の入力地震動の相関性と構造物の組み合わせ応答の関係に関する研究[園]高品質コンクリートの硫酸酸性環境下における耐久性能に関する研究[原田]コンサートホール音場の空間印象評価に関する研究[和久田]Dry-masonry Brick House System as an "Adaptable Building" Model for Asian Markets[Khamidi

THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer

Mesenchymal activation, characterized by dense stromal infiltration of immune and mesenchymal cells, fuels the aggressiveness of colorectal cancers (CRC), driving progression and metastasis. Targetable molecules in the tumor microenvironment (TME) need to be identified to improve the outcome in CRC patients with this aggressive phenotype. This study reports a positive link between high thrombospondin-1 (THBS1) expression and mesenchymal characteristics, immunosuppression, and unfavorable CRC prognosis. Bone marrow-derived monocyte-like cells recruited by CXCL12 are the primary source of THBS1, which contributes to the development of metastasis by inducing cytotoxic T-cell exhaustion and impairing vascularization. Furthermore, in orthotopically generated CRC models in male mice, THBS1 loss in the TME renders tumors partially sensitive to immune checkpoint inhibitors and anti-cancer drugs. Our study establishes THBS1 as a potential biomarker for identifying mesenchymal CRC and as a critical suppressor of antitumor immunity that contributes to the progression of this malignancy with a poor prognosis.大腸がん：骨髄が転移を促進？ --新しい治療法への展望--. 京都大学プレスリリース. 2023-10-27