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Enhanced Cyclic Adenosine Monophosphate Fermentation Production by Aminophylline and Citrate Coupling Addition |
LI Zhi-gang1,2,GU Yang2,TAN Hai2,ZHANG Zhong-hua2,CHANG Jing-ling1,2,*() |
1 Collaborative Innovation Center of Modem Biological Breeding of Henan Province, Xinxiang 453003, China 2 School of Life Science and Technology, Henan Institute of Science and Technology, Xinxiang 453003, China |
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Abstract Objective: The aim of this study is to develop a novel cAMP fermentation process via inhibiting phosphodiesterase activity.Methods: cAMP fermentations with aminophylline addition were conducted in a 7 L fermenter and corresponding fermentation kinetics, key enzymes activities and energy metabolism levels were analyzed. Finally, a fermentation process with aminophylline and citrate coupling added was proposed and conducted for improving cAMP content.Results: Due to 5 mg/L aminophylline added, cAMP concentration was increased by 25.9% with a decrease of 41.6% for coproduct adenosine when compared with those of a control group. There were no obvious deviation for adenylate cyclase and succinyladenylate dehydrogenase activities in the two fermentation batches whereas the activities of phosphodiesterase and 5'-nucleotide enzyme were obvious lower than those of the control group. The energy metabolism analysis results showed that intracellular ATP/AMP were lower than control with an improved AMP level, indicating that ATP synthesis had been the main limited factor for product accumulation. Using the fermentation process with aminophylline and citrate coupling addition, cAMP content achieved 4.48 g/L with 22.1% and 13.8% increasement than those of aminophylline and citrate individual added, and adenosine content was 0.98 g/L with 51.7% and 25.3% lower than individual added.Conclusion: With aminophylline added, the activities of phosphodiesterase and 5'-nucleotide enzyme were inhibited and cAMP content was also improved obviously due to decreased cAMP decomposition and adenosine synthesis. However, the ATP synthesis level had been the main limiting factor for improving cAMP production. The fermentation process with aminophylline and citrate coupling addition could decrease cAMP decomposition and improve energy metabolism simultaneously, which further promoted cAMP fermentation synthesis.
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Received: 11 March 2021
Published: 03 August 2021
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Corresponding Authors:
Jing-ling CHANG
E-mail: changjl001@126.com
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