State Key Laboratory of Materials-Oriented Chemical Engineering, College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 210009, PR China.
Bioresour Technol. 2010 May;101(9):3159-63. doi: 10.1016/j.biortech.2009.12.081. Epub 2010 Jan 12.
Cyclic adenosine monophosphate (cAMP) was synthesized through the purine salvage synthesis pathway by Arthrobacter A302. Results showed that hypoxanthine was the best of the precursors, and the cAMP concentration reached 4.06 g/L. For inhibition of the glycolytic pathway, sodium fluoride was found the optimal effector, which was further studied on cAMP production. With the addition of 0.4 g/L of sodium fluoride, the maximal cAMP concentration reached 11.04 g/L, and the concentrations of lactic acid, alpha-ketoglutarate and citric acid were decreased by 77%, 86% and 76%, respectively. Meanwhile, the specific activities of glyceraldehyde 3-phosphate dehydrogenase, phosphofructokinase and pyruvate kinase were decreased by 66%, 61%, and 46%, respectively. By contrast the activity of 6-phosphoglucose dehydrogenase was increased by 100%, which demonstrated the redistribution of metabolic flux. This is the first study to reveal the regulatory mechanisms of different effectors on cAMP production among the EMP pathway, HMP pathway and TCA cycle.
环磷酸腺苷 (cAMP) 是由节杆菌 A302 通过嘌呤补救合成途径合成的。结果表明，次黄嘌呤是最好的前体，cAMP 浓度达到 4.06 g/L。为了抑制糖酵解途径，发现氟化钠是最佳效应物，并进一步研究了 cAMP 的生产。添加 0.4 g/L 的氟化钠后，cAMP 浓度达到 11.04 g/L，乳酸、α-酮戊二酸和柠檬酸的浓度分别降低了 77%、86%和 76%。同时，甘油醛 3-磷酸脱氢酶、磷酸果糖激酶和丙酮酸激酶的比活力分别降低了 66%、61%和 46%。相比之下，6-磷酸葡萄糖脱氢酶的活性增加了 100%，这表明代谢通量发生了再分配。这是首次研究 EMP 途径、HMP 途径和 TCA 循环中不同效应物对 cAMP 生产的调节机制。
