Metabolic pathway analysis and dynamic macroscopic model development for lovastatin production by Monascus purpureus using metabolic footprinting concept

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.