The insufficient supply of ATP limited cAMP synthesis during fermentations using Arthrobacter sp. CCTCC 2013431. cAMP fermentations with/without hexametaphosphate addition were conducted in a 7 L bioreactor and the underlying mechanism for enhanced cAMP biosynthesis under hexametaphosphate addition condition was investigated. Due to the addition of 2 g/L-broth sodium hexametaphosphate at 24 h, cAMP content reached 3.64 g/L, with an increment of 33.82 % when compared with control. The transcriptome analysis results revealed that 227 genes were up-regulated and 265 genes were down-regulated significantly in response to hexametaphosphate addition. For glycometabolism, the transcription levels of key enzymes genes involved with cAMP synthesis were enhanced significantly, and for energy metabolism, the transcription levels of genes associated with electron transport chain and polyphosphate kinase gene were increased significantly by which sufficient carbon skeleton and ATP were provided for cAMP biosynthesis. In addition, transcription levels of most reductase genes were up regulated significantly suggesting that intracellular antioxidant capacity was improved effectively by hexametaphosphate. Finally, activities of key enzymes together with intracellular contents of ROS, MDA and key metabolites were detected and the results were in accordance to those of transcriptome analysis. It could be concluded that hexametaphosphate relieved severe oxidative stress, strengthened energy metabolism and redistributed the carbon flux among different pathways resulting in enhanced cAMP synthesis and decreased byproduct generation.
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