Objective: To explore the mechanism for enhanced cAMP fermentation production by polyphosphates, Arthrobacter sp. CCTCC 2013431 culture was carried out under low-polyphosphates addition condition as the starting strain. Methods: Fermentations with/without hexametaphosphate addition were conducted in a 7 L bioreactor and the fermentation performance, global gene transcriptome, key enzymes activities together with important metabolites levels were analyzed systematically. Results: With 2 g/L-broth sodium hexametaphosphate added at 24 h, cAMP concentration reached 3.64 g/L with an increment of 33.82% higher than that of control group and the fermentation performance was also promoted obviously. Transcriptome analysis showed that 227 genes were up-regulated significantly and 265 genes were down-regulated significantly due to the addition of hexametaphosphate. For glycometabolism, the transcription levels of key enzyme genes in pentose phosphate pathway and cAMP synthesis pathway were enhanced significantly and for energy metabolism the transcription levels of complex Ⅲ, complex Ⅳ as well as F0F1-ATPase in electron transport chain and polyphosphate kinase gene were also increased significantly by which sufficient carbon skeleton and ATP were provided for cAMP biosynthesis. In addition, transcription levels of reductase genes, such as thioredoxin, catalase and CLP protease, were also increased significantly whereby intracellular redox balance was maintained conducive to cell metabolism and product synthesis. Finally, the activities of pyruvate kinase, 6-phosphoglucose dehydrogenase, adenylosuccinate synthetase, adenylate cyclase, catalase, polyphosphate kinase and intracellular ROS, ATP and NADPH levels under different fermentation conditions were measured to further support the transcriptome analysis results. Conclusion: Sodium hexametaphosphate addition enhanced the carbon flux distribution in pentose phosphate pathway and cAMP synthesis pathway and energy metabolism for ATP synthesis. At the same time, intracellular redox balance was also maintained. Furthermore, cAMP fermentation synthesis and accumulation was promoted significantly.