Abstract Understanding and modeling of the metabolic pathway of a cell by probing the fraction of extracellular metabolites is gaining much interest in biological reactions. This communication deals with metabolic footprinting technique to understand the effect of static- and shake-culture conditions on the production of lovastatin by Monascus purpureus by probing the predominant exometabolites. A strong glycolytic flux pattern was observed in the shake culture of M. purpureus that resulted in the accumulation of tricarboxylic acids such as, citric acid, succinic acid, and oxalic acid, apart from glycerol and ethanol. Interestingly, those exometabolites were most probably utilized for enhanced production of lovastatin in shake culture after 10 days of fermentation. This suggests a correlation with the higher production of lovastatin in shake culture compared to that of in static-culture. The predominant metabolic network was developed from metabolic footprinting technique. Metabolic flux analysis was performed to check the consistency of the proposed metabolic cascade. A reduced dynamic metabolic model was developed from eight elementary macro-reactions. Predicted specific substrate utilization and product excretion rates have also been correlated well with the experimental observations, which validate the proposed metabolic pathway developed from metabolic footprinting data.

中文翻译：

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使用代谢足迹概念的红曲霉生产洛伐他汀的代谢途径分析和动态宏观模型开发

摘要 通过探测细胞外代谢物的分数来理解和模拟细胞的代谢途径，在生物反应中越来越受到关注。本次交流涉及代谢足迹技术，通过探测主要的外代谢物来了解静态和摇动培养条件对红曲霉生产洛伐他汀的影响。在 M. purpureus 的摇动培养物中观察到强烈的糖酵解通量模式，导致除了甘油和乙醇之外的三羧酸（例如柠檬酸、琥珀酸和草酸）的积累。有趣的是，这些外代谢物最有可能在发酵 10 天后用于提高摇动培养中洛伐他汀的产量。这表明与静态培养相比，摇动培养中洛伐他汀的产量更高。主要的代谢网络是从代谢足迹技术发展而来的。进行代谢通量分析以检查提议的代谢级联的一致性。一个简化的动态代谢模型是从八个基本的宏观反应发展而来的。预测的特定底物利用率和产物排泄率也与实验观察密切相关，这验证了从代谢足迹数据开发的拟议代谢途径。一个简化的动态代谢模型是从八个基本的宏观反应发展而来的。预测的特定底物利用率和产物排泄率也与实验观察密切相关，这验证了从代谢足迹数据开发的拟议代谢途径。一个简化的动态代谢模型是从八个基本的宏观反应发展而来的。预测的特定底物利用率和产物排泄率也与实验观察密切相关，这验证了从代谢足迹数据开发的拟议代谢途径。