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The New Strategy of Breeding Cytidine Excessive Biosynthesis Mutants by pyr Operon Rearrangement of Bacillus amyloliquefaciens

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Advances in Applied Biotechnology

Part of the book series: Lecture Notes in Electrical Engineering ((LNEE,volume 333))

Abstract

Cytidine is a good antitumor and antiviral intermediate which can also be used as a healthy food ingredients. With the market for cytidine increasing, the large-scale production of cytidine by microbial fermentation method has become a major way to solve this problem. While improving cytidine production, the regulation of pyr operon is essential to the excessive synthesis cytidine. However, its transcriptional regulation mechanism is unclear. The passage summarizes the regulation of de novo pyrimidine nucleotide biosynthesis (pyr genes) and the metabolic regulation mechanism of cytidine synthesis in Bacillus amyloliquefaciens. This paper makes the regulation protein pyrR as the research object, presents a series of Bacillus amyloliquefaciens pyrimidine operon transcriptional regulatory rearrangement strategy, effects the transcriptional regulation on cytidine biosynthesis, and aims to provide a theoretical basis for cytidine yielding strain.

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References

  1. Bezombes C, Laurent G, Jaffrezou JP et al (2003) Implication of rafe microdomains in drug induced apoptosis. Curr Med Chem Anticancer Agents 3(4):263–270

    Article  CAS  Google Scholar 

  2. Turnbough CL Jr., Switzer RL (2008) Regulation of pyrimidine biosynthetic gene expression in bacteria: repression without repressors. Microbiol Mol Biol Rev 72(2):266–300

    Google Scholar 

  3. Caldara M, Dupont G, Leroy F, Goldbeter A, Vuyst LD, Cunin R (2008) Arginine biosynthesis in Escherichia coli experimental perturbation and mathematical modeling. J Biol Chem 283(10):6347–6358

    Article  CAS  Google Scholar 

  4. Song KH, Do YK, Sang YK, Jung KL, Hyung HH (2005) Thymidine production by Corynebacterium ammoniagenes mutants. Microbiol Biotechnol 15(3):477–483

    CAS  Google Scholar 

  5. Lee HC, Ahn JM, Lee SN, Kim JH (2004) Overproduction of thymidine by recombinant Brevibacterium helvolum amplified with cytidine monophosphate phosphohydrolase gene from bacteriophage PBS2. Biotechnol Lett 26:265–268

    Article  CAS  Google Scholar 

  6. Palmen LG, Becker K, Bulow L, Kvassman JO (2008) A double role for a strictly conserved serine: further insights into the dUTPase catalytic mechanism. Biochemistry 47:7863–7874

    Article  Google Scholar 

  7. Lee HC, Kim JH, Kim JS, Jang W, Kim SY (2009) Fermentative production of thymidine by a metabolically engineered Escherichia coli strain. Appl Environ Microbiol 75(8):2423–2432

    Google Scholar 

  8. Rabinowitz JD, Hsiao JJ, Gryncel KR, Kantrowitz ER, Feng XJ, Li GY, Rabitz H (2008) Dissecting enzyme regulation by multiple allosteric effectors: nucleotide regulation of aspartate transcarbamoylase. Biochemistry 47(21):5881–5888

    Article  CAS  Google Scholar 

  9. Koo BS, Hyun HH, Kim SY, Kim CH, Lee HC (2011) Enhancement of thymidine production in E. coli by eliminating repressors regulating the carbamoyl phosphate synthetase operon. Biotechnol Lett 33:71–78

    Article  CAS  Google Scholar 

  10. Zhang H, Switzer RL (2003) Transcriptional pausing in the Bacillus subtilis PyrR with pyr mRNA by site-directed mutagenesis of the protein. J Bacteriol 185:4764–4771

    Article  CAS  Google Scholar 

  11. Switzer RL (2009) Discoveries in bacterial nucleotide metabolism. J Biol Chem 284(11):6585–6594

    Article  CAS  Google Scholar 

  12. Lee HC, Kim JS, Jang W, Kim SY (2010) High NADPH/NADP + ratio improves thymidine production by a metabolically engineered Escherichia coli strain. J Biotechnol 149:24–32

    Article  CAS  Google Scholar 

  13. Fang H, Xie X, Xu Q, Zhang C, Chen N (2012) Effects of medium components and fermentation conditions on cytidine production by recombinant Escherichia coli CYT20. Lect Notes Electr Eng 249:15–22

    Google Scholar 

  14. Fang H, Zhang C, Xie X, Xu Q, Zhou Y, Chen N (2014) Enhanced cytidine production by a recombinant Escherichia coli strain using genetic manipulation strategies. Ann Microbiol 64(3):1203–1210

    Google Scholar 

  15. Fang H, Liu H, Chen N, Zhang C, Xie X, Xu Q (2013) Site-directed mutagenesis studies on the uridine monophosphate binding sites of feedback inhibition in carbamoyl phosphate synthetase and effects on cytidine production by Bacillus amyloliquefaciens. Can J Microbiol 59(6):374–379

    Google Scholar 

  16. Switzer RL, Turner RJ, Lu Y (1999) Regulation of the Bacillus subtilis pyrimidine biosynthetic operon by transcriptional attenuation: control of gene expression by an mRNA-binding protein. Prog Nucleic Acids Res Mol Biol 62:329–367

    Article  CAS  Google Scholar 

  17. Arsene-Ploetz F, Kugler V, Martinussen J, Bringel F (2006) Expression of the pyroperon of Lactobacillus plantarumis regulated by inorganic carbon availability through a second regulator, PyrR2, homologous to the pyrimidine regulator PyrR. J Bacteriol 188:8607–8616

    Article  Google Scholar 

  18. Nicoloff H, Elagoz A, Arsene-Ploetze F, Kammerer B, Martinussen J, Bringel F (2005) Repression of the pyr operon in Lactobacillus plantarum prevents its ability to grow at low carbon dioxide levels. J Bacteriol 187:2093–2104

    Article  CAS  Google Scholar 

  19. Martinussen J, Schallert J, Andersen B, Hammer K (2001) The pyrimidine operon pyrRPB-carA from Lactococcus lactis. J Bacteriol 183:2785–2794

    Article  CAS  Google Scholar 

  20. Ghim SY, Kim CC, Bonner ER, D’Elia JN, Grabner GK, Switzer RL (1999) The Enterococcus faecalis pyr operon is regulated by autogenous transcriptional attenuation at a single site in the 5’leader. J Bacteriol 181:1324–1329

    CAS  Google Scholar 

  21. Seul K-J, Cho H-S, Ghim S-Y (2011) Characterization of a PyrR-deficient mutant of Bacillus subtilis by a proteomic approach. Korean J Microbiol Biotechnol 39(1):9–19

    CAS  Google Scholar 

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Acknowledgments

We thank our colleagues for critical reading of the manuscript and providing valuable suggestions. This work was supported by Chinese National Natural Science Foundation (Grant №31301542).

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Correspondence to Haitian Fang .

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Wu, Q., Liu, H., Fang, H., He, J., He, X., Yu, L. (2015). The New Strategy of Breeding Cytidine Excessive Biosynthesis Mutants by pyr Operon Rearrangement of Bacillus amyloliquefaciens . In: Zhang, TC., Nakajima, M. (eds) Advances in Applied Biotechnology. Lecture Notes in Electrical Engineering, vol 333. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46318-5_68

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