Abstract
Arthrobacter sp. CGMCC 3584 is able to produce high yields of extracellular cyclic adenosine monophosphate (cAMP), which plays a vital role in the field of treatment of disease and animal food, during aerobic fermentation. However, the molecular basis of cAMP production in Arthrobacter species is rarely explored. Here, for the first time, we report the comparative transcriptomic and proteomic study of Arthrobacter cells to elucidate the higher productivity of cAMP under high oxygen supply. We finally obtained 14.1% and 19.3% of the Arthrobacter genome genes which were up-regulated and down-regulated notably, respectively, with high oxygen supply, and identified 54 differently expressed proteins. Our results revealed that high oxygen supply had two major effects on metabolism: inhibition of glycolysis, pyruvate metabolism, nitrogen metabolism, and amino acid metabolism (histidine, branched-chain amino acids and glutamate metabolism); enhancement of the tricarboxylic acid cycle and purine metabolism. We also found that regulation of adenylate cyclase and phosphodiesterase was not significant under high oxygen supply, suggesting efficient cAMP export might be important in cAMP production. These findings may contribute to further understanding of capacities of Arthrobacter species and would be highly useful in genetic regulation for desirable production.
Highlights
Cyclic adenosine monophosphate is an important compound which exists in many living cells, and participates in the regulation of physiological actions, such as cell proliferation and differentiation, hormones synthesis and secretion, membrane protein activity, nervous activity, gene expression and so on[1,2,3]
Mass spectrum (MS) based proteomic analysis of Arthrobacter cells cultured under various oxygen supply conditions was conducted to dissect the molecular regulatory mechanism of cyclic adenosine monophosphate (cAMP) production
The final cAMP yield on DCW reached 0.57 ± 0.027 g/g DCW and 1.02 ± 0.03 g/g DCW under low and high oxygen supply respectively. This result showed that the oxygen supply condition had a greater influence on cAMP production than cell growth
Summary
Cyclic adenosine monophosphate (cAMP) is an important compound which exists in many living cells, and participates in the regulation of physiological actions, such as cell proliferation and differentiation, hormones synthesis and secretion, membrane protein activity, nervous activity, gene expression and so on[1,2,3]. Mass spectrum (MS) based proteomic analysis of Arthrobacter cells cultured under various oxygen supply conditions was conducted to dissect the molecular regulatory mechanism of cAMP production. A microarray study on Kluyveromyces lactis showed that the availability of oxygen determined the fermentation pattern, with increasing the glucose metabolism and reducing fluxes in the pentose phosphate pathway under oxygen-limited conditions[14]. Another DNA microarray analysis of the full transcriptome of the Bordetella pertussis bacterium revealed that oxygen limitation during cultivation had a fully reversible effect on gene expression. We try to comprehensively explore the underlying mechanisms of oxygen supply on cAMP biosynthesis, which will help to better understand the metabolic regulation mechanism of Arthrobacter species and provide valuable information for further improvement of cAMP production
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