Enhanced cyclic adenosine monophosphate production by Arthrobacter A302 through rational redistribution of metabolic flux

Chen, Xiaochun; Song, He; Fang, Ting; Cao, Jiaming; Ren, Huajing; Bai, Jianxin; Xiong, Jing; Ouyang, Pingkai; Ying, Hanjie

doi:10.1016/j.biortech.2009.12.081

Cited by 18 publications

(10 citation statements)

References 33 publications

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“…The pH decreased from the initial value of 7.0-6.10, and then gradually increased to approximately 6.40 at the end of the culturing process. The pH trend during fermentation was in agreement with the findings of Chen et al (2010). This decline in medium pH was likely caused by organic acids (such as pyruvate, citrate, or a-ketoglutarate) generated from glucose utilization during the growth phase.…”

Section: Resultssupporting

confidence: 85%

“…When glucose is substituted for sucrose in the fermentation medium for cAMP biosynthesis by Streptomyces antibioticus, the pH of the culture broth becomes more acidic, and cAMP synthesis and excretion from the mycelium increases by a factor of 1.5-3 (Lishnevskaia et al 1986). Chen et al (2010) reported that high levels of organic acids are produced by Arthrobacter sp. A302, greatly reducing cAMP production.…”

Section: Introductionmentioning

confidence: 99%

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Production of cyclic adenosine monophosphate by Arthrobacter sp. A302 using fed-batch fermentation with pH-shift control

Cao

Chen

Ren

et al. 2011

World J Microbiol Biotechnol

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The production of cyclic adenosine monophosphate (cAMP) by Arthrobacter sp. A302 was studied in a 5 L stirred tank fermentor under a range of pH values (6.5-8.0) and glucose feeding rates. In batch fermentation under a controlled pH, the optimum pH for cell growth was 7.5 with dry cell density (X) of 11.43 g L, and the optimum pH for cAMP accumulation was 7.0 with cAMP concentration of 7.41 g L. In order to achieve the high X and cAMP yield simultaneously, a pH-shift control strategy was proposed based on kinetic analysis of specific cell growth rate (μ) and specific cAMP formation rate (q ( s )). In this method, pH was controlled to 7.0 for the first 30 h of fermentation, and then subsequently shifted to 7.5 and maintained until the end of the process. Application of this approach significantly enhanced the cAMP concentration. Thereafter, cAMP production was further improved by combining the above-mentioned pH-control system and fed-batch process with glucose at a constant feeding rate of 1.0 g L(-1 )h(-1). Under optimum conditions, the final cAMP production was 10.87 g L, which is 110.0, 46.7, and 27.7% higher than that of the pH-uncontrolled, pH-controlled, and pH-shift controlled methods, respectively.

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Section: Resultssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Production of cyclic adenosine monophosphate by Arthrobacter sp. A302 using fed-batch fermentation with pH-shift control

Cao

Chen

Ren

et al. 2011

World J Microbiol Biotechnol

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“…Consequently, decreased activity of PYK resulted in an increase in phosphoenolpyruvic acid concentration (as shown in Table ) and a reduction in pyruvate and acetate concentrations, which was in good agreement with the published evidence (Chen et al . ). Furthermore, the increase in PEP concentration inhibited phosphofructokinase activity directly.…”

Section: Resultsmentioning

confidence: 97%

Efficient biosynthesis ofd-ribose using a novel co-feeding strategy inBacillus subtiliswithout acid formation

Cheng

Zhuang

et al. 2016

Lett Appl Microbiol

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Bacillus subtilis usually produce d-ribose accompanied by plenty of organic acids when glucose is used as a carbon source, which is considered to be a consequence of mismatched glycolytic and tricarboxylic acid cycle capacities. This is the first study to provide high-efficiency biosynthesis of d-ribose without organic acid formation in B. subtilis, which would be lower than the cost of separation and purification. The strain transketolase-deficient B. subtilis CGMCC 3720 can be potentially applied to the production of d-ribose in industry.

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“…Report found that 14.93 g/L of cAMP was produced with a conversion rate of 91.5% when pyruvate sodium was used to be enzyme activator for 6 hr in Escherichia coli (Li et al, 2013). It also found that the addition of 0.4 g/L of sodium fluoride in Arthrobacter A302, the maximal cAMP concentration reached 11.04 g/L (Chen et al, 2010). Report also showed a simple and an efficient enzymatic synthesis of cAMP from ATP using Bordetella pertussis adenylate cyclase coimmobilized on CNBr-activated agarose beads with its activator, calmodulin (Bellalou, Sarfati, Predeleanu, Ladant, & Bǎrzu, 1988).…”

Section: Introductionmentioning

confidence: 98%

Construction of industrial baker’s yeast with high level of cAMP

Dong

Wang

et al. 2019

J Food Biochem

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Cyclic adenosine monophosphate (cAMP) plays an important role in modulating the activity of microbe cell. In this study, PKA (protein kinase A) activity was weakened through truncation of TPK2 promoter (−150 bp and −300 bp) and gene deletion of BCY1 (encodes the regulatory subunit of PKA), TPK1 and TPK3, generating strains BY9a‐T2‐150 and BY9a‐T2‐300, respectively. High‐performance liquid chromatography analysis showed cAMP levels in BY9a‐T2‐150 and BY9a‐T2‐300 were increased by 5‐ and 18‐fold, respectively, compared with that of parent strain, BY9a. The expression levels of TPK2 gene in two engineered strains were decreased by 95% and 97% compared with that of BY9a, respectively. The PKA activity reflected by heat resistance of engineered strains enhanced compared with parent strain BY9a. This study show a new method to increase the intracellular cAMP concentration in industrial yeast by fine‐tuning of PKA activity, without influence in growth and fermentation properties. Practical applications cAMP as the “second messenger,” is essential for plant, animal, and microorganisms and human life. But its synthesis is still limited by expensive cost and time‐consuming method. We constructed the industrial baker’s yeast with high level of cAMP and desired to be used to produce functional food for relaxing smooth muscle, expanding blood vessels, improving liver function, and promoting nerve regeneration and as a food additive for treating hyperthyreosis and hepatopathy. The methods of two step homologous recombination and backcross operated in this study eliminate the exogenous gene in engineered strains, made it safety to be used in food production. Fine‐tuning of PKA activity in engineered strains ensure produce high level of cAMP and exhibit normal growth performance in engineering strains. Therefore, this work is significant in functional foods product and has the potential to be used in practical application.

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Enhanced cyclic adenosine monophosphate production by Arthrobacter A302 through rational redistribution of metabolic flux

Cited by 18 publications

References 33 publications

Production of cyclic adenosine monophosphate by Arthrobacter sp. A302 using fed-batch fermentation with pH-shift control

Production of cyclic adenosine monophosphate by Arthrobacter sp. A302 using fed-batch fermentation with pH-shift control

Efficient biosynthesis ofd-ribose using a novel co-feeding strategy inBacillus subtiliswithout acid formation

Construction of industrial baker’s yeast with high level of cAMP

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