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Impact of nitrogen concentration on validamycin A production and related gene transcription in fermentation of Streptomyces hygroscopicus 5008

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Abstract

Validamycin A (VAL-A) is an important and widely used agricultural antibiotic. In this study, statistical screening designs were applied to identify significant medium variables for VAL-A production and to find their optimal levels. The optimized medium caused 70% enhancement of VAL-A production. The difference between optimized medium and original medium suggested that low nitrogen source level might attribute to the enhancement of VAL-A production. The addition of different nitrogen sources to the optimized medium inhibited VAL-A production, which confirmed the importance of nitrogen concentration for VAL-A production. Furthermore, differences in structural gene transcription and enzyme activity between the two media were assayed. The results showed that lower nitrogen level in the optimized medium could regulate VAL-A production in gene transcriptional level. Our previous study indicated that the transcription of VAL-A structural genes could be enhanced at elevated temperature. In this work, the increased fermentation temperature from 37 to 42 °C with the optimized medium enhanced VAL-A production by 39%, which testified to the importance of structural gene transcription in VAL-A production. The information is useful for further VAL-A production enhancement.

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References

  1. Lin JX, Bai LQ, Deng ZX, Zhong JJ (2011) Enhanced production of ansamitocin P-3 by addition of isobutanol in fermentation of Actinosynnema pretiosum. Bioresour Technol 102:1863–1868

    Article  CAS  Google Scholar 

  2. Trong KV, Gray PP (1987) Influence of ammonium on the biosynthesis of the macrolide antibiotic tylosin. Enzyme Microb Technol 9:590–593

    Article  Google Scholar 

  3. Lebrihi A, Lamsaif D, Lefebvre G, Gernain P (1992) Effect of ammonium ions on spiramycin biosynthesis in Streptomyces ambofaciens. Appl Microbiol Biotechnol 37:382–387

    Article  CAS  Google Scholar 

  4. Brafia AF, Wolfe S, Demain AL (1985) Ammonium repression of cephalosporin production by Streptomyces clavuligerus. Can J Microbiol 31:736–743

    Article  Google Scholar 

  5. Zhu CH, Lu FP, He YN, Han ZL, Du LX (2007) Regulation of validamycin biosynthesis in Streptomyces virdochromogenes: effect of glucose, ammonium ion, and inorganic phosphate. Appl Microbiol Biotechnol 73:1031–1038

    Article  CAS  Google Scholar 

  6. Hesketh A, Sun J, Bibb M (2001) Induction of ppGpp synthesis in Streptomyces coelicolor A3(2) grown under conditions of nutritional sufficiency elicits actII-ORF4 transcription and actinorhodin biosynthesis. Mol Microbiol 39:136–144

    Article  CAS  Google Scholar 

  7. Yu Y, Bai LQ, Minagawa K, Jian X, Li L, Li J, Chen S, Deng ZX (2005) Gene cluster responsible for validamycin biosynthesis in Streptomyces hygroscopicus subsp. jinggangensis 5008. Appl Environ Microbiol 71:5066–5507

    Article  CAS  Google Scholar 

  8. Bai LQ, Li L, Xu H, Minagawa K, Yu Y, Zhang Y, Zhou XF, Deng ZX (2006) Functional analysis of the validamycin biosynthetic gene cluster and engineered production of Validoxylamine A. Chem Biol 13:387–397

    Article  CAS  Google Scholar 

  9. Liao YQ, Wei ZH, Bai LQ, Deng ZX, Zhong JJ (2009) Effect of fermentation temperature on validamycin A production by Streptomyces hygroscopicus 5008. J Biotechnol 142:271–274

    Article  CAS  Google Scholar 

  10. Wei ZH, Bai LQ, Deng ZX, Zhong JJ (2011) Enhanced production of validamycin A by H2O2-induced reactive oxygen species in fermentation of Streptomyces hygroscopicus 5008. Bioresour Technol 102:1783–1787

    Article  CAS  Google Scholar 

  11. Xu H, Yang JT, Bai LQ, Deng ZX, Mahmud T (2008) Genetically engineered production of 1,1′-bis-valienamine and validienamycin in Streptomyces hygroscopicus and their conversion to valienamine. Appl Microbiol Biotechnol 81:895–902

    Article  Google Scholar 

  12. Zheng YG, Xue YP, Shen YC (2006) Production of valienamine by newly isolated strain: Stenotrophomonas maltrophilia. Enzyme Microb Technol 39:1060–1065

    Article  CAS  Google Scholar 

  13. Kieser T, Bibb MJ, Chater KF, Butter MJ, Hopwood DA (2000) Practical Streptomyces genetics: a laboratory manual. John Innes Foundation, Norwich, pp 342–453

    Google Scholar 

  14. Deutsch J (1983) Glucose-6-phosphate dehydrogenase, 3rd edn., Methods of enzymatic analysisVerlag Chemie, Germany, pp 191–197

    Google Scholar 

  15. Li JH, Liu L, Fang J, Du GC, Chen J (2009) Statistical modeling and optimization for enhanced whole-cell biotransformation synthesis of 2-O-alpha-d-glucopyranosyl-l-ascorbic acid from maltose and l-ascorbic acid by Aspergillus niger capable of producing alpha-glucosidase. J Biosci Bioeng 108:26–127

    Article  Google Scholar 

  16. Li JH, Liu L, Wu J, Sun J, Du GC, Chen J, Tao WY (2010) Modeling and optimization of cutinase production by recombinant Escherichia coli based on statistical experimental designs. Korean J Chem Eng 27:1233–1238

    Article  CAS  Google Scholar 

  17. Ma FX, Kim JH, Kim SB, Seo YG, Chang YK, Hong SK, Kim CJ (2008) Medium optimization for enhanced production of Rifamycin B by Amycolatopsis mediterranei S699: combining a full factorial design and a statistical approach. Process Biotechnol 43:954–960

    Article  CAS  Google Scholar 

  18. Jian XH, Pang XH, Yu Y, Zhou XF, Deng ZX (2006) Identification of genes necessary for jinggangmycin biosynthesis from Streptomyces hygroscopicus 10–22. Anton Leeuw Int J G 90:29–39

    Article  CAS  Google Scholar 

  19. Dong H, Mahmud T, Tornus I, Lee S, Floss HG (2001) Biosynthesis of the validamycins: identification of intermediates in the biosynthesis of validamycin A by Streptomyces hygroscopicus var. limoneus. J Am Chem Soc 123:2733–2742

    Article  CAS  Google Scholar 

  20. Tarhan L, Kayal HA, Sazak A, Şahin N (2011) The Correlations between TCA-Glyoxalate metabolite and antibiotic production of Streptomyces sp. M4018 grown in glycerol, glucose, and starch mediums. Appl Biochem Biotechnol 164:318–337

    Article  CAS  Google Scholar 

  21. Lian W, Jayaoal KP, Charaniya S, Mehra S, Glod F, Kyung YS, Sherman DH, Hu WS (2008) Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2). BMC Genomics 9:56

    Article  Google Scholar 

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Acknowledgments

We appreciate the financial support from the National 863 High Technology Program (Project # 2006AA10A202) of the MOST and the National Natural Science Foundation of China (NSFC project No. 30821005). JJZ also appreciates the National 985 Project and the University Distinguished Professorship program (SJTU).

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China

    Zhen-Hua Wei & Jian-Jiang Zhong

  2. State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China

    Linquan Bai, Zixin Deng & Jian-Jiang Zhong

Authors
  1. Zhen-Hua Wei
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  2. Linquan Bai
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  3. Zixin Deng
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  4. Jian-Jiang Zhong
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Correspondence to Jian-Jiang Zhong.

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Wei, ZH., Bai, L., Deng, Z. et al. Impact of nitrogen concentration on validamycin A production and related gene transcription in fermentation of Streptomyces hygroscopicus 5008. Bioprocess Biosyst Eng 35, 1201–1208 (2012). https://doi.org/10.1007/s00449-012-0707-3

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  • DOI: https://doi.org/10.1007/s00449-012-0707-3

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