Enhanced cyclic adenosine monophosphate production by Arthrobacter A302 through rational redistribution of metabolic flux.
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.
Chen
Xiao-chun
XC
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 210009, PR China.
Song
He
H
Fang
Ting
T
Cao
Jia-ming
JM
Ren
Hua-jing
HJ
Bai
Jian-xin
JX
Xiong
Jian
J
Ouyang
Ping-kai
PK
Ying
Han-jie
HJ
D001173:Arthrobacter / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D002264:Carboxylic Acids / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D005285:Fermentation / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D012969:Sodium Fluoride / Q000494:pharmacology
D002264:Carboxylic Acids; D012969:Sodium Fluoride; D000242:Cyclic AMP