Skip to main content

Enhanced Adenosine Production by Bacillus subtilis at Condition with Comprehensively Controlled Dissolved Oxygen and pH During Fermentation

  • Conference paper
  • First Online:
Advances in Applied Biotechnology

Part of the book series: Lecture Notes in Electrical Engineering ((LNEE,volume 332))

Abstract

Adenosine has potent effects on cardiovascular diseases and has been widely used as an antiarrhythmic agent. To improve its production, we investigated the effects of dissolved oxygen (DO) and pH on production by Bacillus subtilis. Based on the kinetic parameters at different DO levels, we proposed a two-stage DO strategy to control DO level at 30–40 % before 20 h of fermentation and 10–20 % after 20 h of fermentation, and confirmed that using this strategy could increase adenosine yield to 19.2 g/L in 52 h, which is increased by 78.6, 66.7, 9.5, 18.6, and 32.2 %, compared to the conditions with DO uncontrolled or controlled at 0–10, 10–20, 20–30, and 30–40 %, respectively. On this basis, pH was adjusted to further boost adenosine production. The results showed that the two-stage DO plus pH-shift method was the optimal way for adenosine production, under which, adenosine yield was further improved by 21.4 %, reaching 23.3 g/L at 56 h. To our knowledge, this is the first report on adenosine production verifying that the two-stage DO plus pH-shift method is effective for enhancing adenosine yield by B. subtilis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mallet M (2004) Proarrhythmic effects of adenosine: a review of the literature. Emerg Med J 21:408–410

    Article  CAS  Google Scholar 

  2. Kunst F, Ogasawara N, Moszer I et al (1997) The complete genome sequence of the gram-positive bacterium Bacillus subtilis. Nature 390:249–256

    Article  CAS  Google Scholar 

  3. Sauer U, Cameron DC, Baily JE (1998) Metabolic capacity of Bacillus subtilis for the production of purine nucleosides, riboflavin, and folic acid. Biotechnol Bioeng 59:227

    Article  CAS  Google Scholar 

  4. Schallmey M, Singh A, Ward OP (2004) Developments in the use of Bacillus species for industrial production. Can J Microbiol 50:1–17

    Article  CAS  Google Scholar 

  5. Karasawa M, Ichiumi T, Nakamatsu W (1992) Manufacture of adenosine with Bacillus. JP 04030797 A2

    Google Scholar 

  6. Nishiyama T, Karasawa M, Yamamoto K et al (1995) Production of adenosine by a growth-improved mutant of Bacillus subtilis. Industrial production of adenosine.III. Nippon Nogei Kagaku Kaishi 69:1341–1347

    Article  CAS  Google Scholar 

  7. Nakamatsu W, Nishiyama T, Ichiumi T et al (1985) Adenosine by bacterial fermentation. JP 60176596 A2

    Google Scholar 

  8. Nishiyama T, Nakamatsu T, Shirota T (1994) Adenosine production by a mutant of Bacillus subtilis resistant to adenine analogs. Industrial production of adenosine.II. Nippon Nogei Kagaku Kaishi 68:809–814

    Article  CAS  Google Scholar 

  9. Kaya-Çeliker H, Angardi V, Çalık P (2009) Regulatory effects of oxygen transfer on overexpression of recombinant benzaldehyde lyase production by Escherichia coli BL21 (DE3). Biotechnol J 4:1066–1076

    Article  Google Scholar 

  10. Liu YS, Wu JY, Ho KP (2006) Characterization of oxygen transfer conditions and their effects on Phaffia rhodozyma growth and carotenoid production in shake-flask cultures. Biochem Eng J 27:331–335

    Article  Google Scholar 

  11. Li H, Chen Y, Gu G (2008) The effect of propionic to acetic acid ratio on anaerobic–aerobic (low dissolved oxygen) biological phosphorus and nitrogen removal. Bioresour Technol 99:4400–4407

    Article  CAS  Google Scholar 

  12. Yegneswaran P, Gray M, Thompson B (1991) Effect of dissolved oxygen control on growth and antibiotic production in Streptomyces clavuligerus fermentations. Biotechnol Prog 7:246–250

    Article  CAS  Google Scholar 

  13. Yu WB, Gao SH, Yin CY, Zhou Y, Ye BC (2011) Comparative transcriptome analysis of Bacillus subtilis responding to dissolved oxygen in adenosine fermentation. PLoS ONE 6:e20092. doi:10.1371/journal.pone.0020092

    Article  CAS  Google Scholar 

  14. Feng X, Xu H, Yao J, Li S, Zhu H, Ouyang P (2010) Kinetic analysis and pH-shift control strategy for propionic acid production with Propionibacterium freudenreichii CCTCC M207015. Appl Biochem Biotechnol 160:343–349

    Article  CAS  Google Scholar 

  15. Çalik P, Bilir E, Çalik G, Özdamar TH (2003) Bioreactor operation parameters as tools for metabolic regulations in fermentation processes: influence of pH conditions. Chem Eng Sci 58:759–766

    Article  Google Scholar 

  16. Haneda K, Hirano A, Kodaira R, Ohuchi S (1971) Accumulation of nucleic acid-related substances by microorganisms. Agric Biol Chem 35:1906–1912

    Article  CAS  Google Scholar 

  17. Haneda K, Komatsu K, Kodaira R, Ohsawa H (1972) Stabilization of adenosine-producing mutants derived from Bacillus sp. No. 1043. Agric Biol Chem 36:1453–1460

    Google Scholar 

  18. Cao J, Chen X, Ren H, Zhang J, Li L, Chen Y, Xiong J, Bai J, Ying H (2012) Production of cyclic adenosine monophosphate by Arthrobacter sp. A302 using fed-batch fermentation with pH-shift control. World J Microbiol Biotechnol 28:121–127

    Article  CAS  Google Scholar 

  19. Meiying Z, Guocheng D, Jian C (2002) pH control strategy of batch microbial transglutaminase production with Streptoverticillium mobaraense. Enzyme Microb Technol 31:477–481

    Article  Google Scholar 

  20. Peng Z, Fang J, Li J, Liu L, Du G, Chen J, Wang X, Ning J, Cai L (2010) Combined dissolved oxygen and pH control strategy to improve the fermentative production of L-isoleucine by Brevibacterium lactofermentum. Bioprocess Biosyst Eng 33:339–345

    Article  CAS  Google Scholar 

  21. Shu CH, Liao CC (2002) Optimization of L-phenylalanine production of Corynebacterium glutamicum under product feedback inhibition by elevated oxygen transfer rate. Biotechnol Bioeng 77:131–141

    Article  CAS  Google Scholar 

  22. Huang WC, Chen SJ, Chen TL (2006) The role of dissolved oxygen and function of agitation in hyaluronic acid fermentation. Biochem Eng J 32:239–243

    Article  CAS  Google Scholar 

  23. Peña C, Trujillo-Roldán MA, Galindo E (2000) Influence of dissolved oxygen tension and agitation speed on alginate production and its molecular weight in cultures of Azotobacter vinelandii. Enzyme Microb Technol 27:390–398

    Article  Google Scholar 

  24. Li L, Chen X, Cheng J, Zhang C, Bai J, Chen Y, Niu H, Ying H (2012) Bi-stage control of dissolved oxygen to enhance cyclic adenosine monophosphate production by Arthrobacter A302. Bioprocess Biosyst Eng 35:1281–1286

    Article  CAS  Google Scholar 

  25. Chen XC, Song H, Fang T, Cao JM, Ren HJ, Bai JX, Xiong J, Ouyang PK, Ying HJ (2010) Enhanced cyclic adenosine mono-phosphate production by Arthrobacter A302 through rational redistribution of metabolic flux. Bioresour Technol 101:3159–3163

    Google Scholar 

  26. Liu YP, Zheng P, Sun ZH, Ni Y, Dong JJ, Wei P (2008) Strategies of pH control and glucose-fed batch fermentation for production of succinic acid by Actinobacillus succinogenes CGMCC1593. J Chem Technol Biotechnol 83:722–772

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the excellent support of Shanshan Du in their operation of the fermentation process control. This investigation is supported by the National Natural Science Foundation of China (31100054) and by Program for Changjiang Scholars and Innovative Research Team in University (IRT 1166).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Ning Chen or Xixian Xie .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Liu, Y., He, J., Xu, Q., Zhang, C., Chen, N., Xie, X. (2015). Enhanced Adenosine Production by Bacillus subtilis at Condition with Comprehensively Controlled Dissolved Oxygen and pH During Fermentation. In: Zhang, TC., Nakajima, M. (eds) Advances in Applied Biotechnology. Lecture Notes in Electrical Engineering, vol 332. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45657-6_46

Download citation

Publish with us

Policies and ethics