Skip to main content

Advertisement

SpringerLink
Log in

Improvement of Ansamitocin P-3 Production by Actinosynnema mirum with Fructose as the Sole Carbon Source

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Ansamitocin P-3 (AP-3) is an active and potent anti-tumor maytansinoid, which is usually produced by Actinosynnema spp. In this study, the effects of different carbon sources on biomass and AP-3 production by Actinosynnema mirum were investigated. The results showed great biomass production behavior of A. mirum in glucose medium comparatively to other carbon sources. Interestingly, when fructose was used as the sole carbon source, the highest yield of AP-3 was obtained, which was about fourfold than that of strain cultured in glucose after 168 h. Further analysis conducted in regard to better understanding of such observations in glucose and fructose defined media showed that fructose improves AP-3 production through the stimulation of the key genes of the secondary metabolism pathways. It was concluded that fructose could be a potential carbon source for cost-effective production of AP-3 from an industrial point of view.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Higashide, E., Asai, M., Ootsu, K., Tanida, S., Kozai, Y., Hasegawa, T., Kishi, T., Sugino, Y., & Yoneda, M. (1977). Ansamitocin, a group of novel maytansinoid antibiotics with antitumour properties from Nocardia. Nature Reviews Microbiology, 270, 721–722.

    CAS  Google Scholar 

  2. Cassady, J. M., Chan, K. K., Floss, H. G., & Leistner, E. (2004). Recent developments in the maytansinoid antitumor agents. Chemical and Pharmaceutical Bulletin, 52(1), 1–26.

    Article  CAS  Google Scholar 

  3. Kirschning, A., Harmrolfs, K., & Knobloch, T. (2008). The chemistry and biology of the maytansinoid antitumor agents. Comptes Rendus Chimie, 11(11), 1523–1543.

    Article  CAS  Google Scholar 

  4. Murao, S., Imafuku, S., & Oyama, H. (1997). Isolation of propioxatin A from Actinosynnema sp. SI-23 during a screening for Serratia piscatorum metalloproteinase inhibitors. Bioscience, Biotechnology, and Biochemistry, 61(3), 561–562.

    Article  CAS  Google Scholar 

  5. Yu, T. W., Bai, L., Clade, D., Hoffmann, D., Toelzer, S., Trinh, K. Q., Xu, J., Moss, S. J., Leistner, E., & Floss, H. G. (2002). The biosynthetic gene cluster of the maytansinoid antitumor agent ansamitocin from Actinosynnema pretiosum. Proceedings of the National Academy of Sciences of the United States of America, 99(12), 7968–7973.

    Article  CAS  Google Scholar 

  6. Hatano, K., Mizuta, E., Akiyama, S., Higashide, E., & Nakao, Y. (1985). Biosynthetic origin of the ansa-structure of ansamitocin P-3. Agricultural and Biological Chemistry, 49(2), 327–333.

    Article  CAS  Google Scholar 

  7. Rude, M. A., & Khosla, C. (2006). Production of ansamycin polyketide precursors in Escherichia coli. Journal of Antibiotics, 59(8), 464–470.

    Article  CAS  Google Scholar 

  8. Hasegawa, T., Tanida, S., Hatano, K., Higashide, E., & Yoneda, M. (1983). Motile Actinomycetes: Actinosynnema pretiosum subsp. pretiosum sp. nov., subsp. nov., and Actinosynnema pretiosum subsp. auranticum subsp. nov. International Journal of Systematic Bacteriology, 33(2), 314–320.

    Article  Google Scholar 

  9. Tanida, S., Hasegawa, T., Hatano, K., Higashide, E., & Yoneda, M. (1980). Ansamitocins, maytansinoid antitumor antibiotics. Producing organism, fermentation, and antimicrobial activities. Journal of Antibiotics, 33(2), 192–198.

    Article  CAS  Google Scholar 

  10. Labeda, D., Hatano, K., Kroppenstedt, R., & Tamura, T. (2001). Revival of the genus Lentzea and proposal for Lechevalieria gen. nov. International Journal of Systematic and Evolutionary Microbiology, 51(3), 1045–1050.

    Article  CAS  Google Scholar 

  11. Land, M., Lapidus, A., Mayilraj, S., Chen, F., Copeland, A., Del Rio, T. G., Nolan, M., Lucas, S., Tice, H., & Cheng, J. F. (2009). Complete genome sequence of Actinosynnema mirum type strain (101T). Standards in Genomic Sciences, 1(1), 46–53.

    Article  Google Scholar 

  12. Kayali, H. A., Tarhan, L., Sazak, A., & Sahin, N. (2011). Carbohydrate metabolite pathways and antibiotic production variations of a novel Streptomyces sp. M3004 depending on the concentrations of carbon sources. Applied Biochemistry and Biotechnology, 165(1), 369–381.

    Article  CAS  Google Scholar 

  13. Hodge, J. (1962). Determination of reducing sugars and carbohydrates. Methods in Carbohydrate Chemistry, 1, 380–394.

    CAS  Google Scholar 

  14. Lin, J., Bai, L., Deng, Z., & Zhong, J. J. (2011). Enhanced production of ansamitocin P-3 by addition of isobutanol in fermentation of Actinosynnema pretiosum. Bioresource Technology , 102(2), 1863–1868.

    Article  CAS  Google Scholar 

  15. Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72(1–2), 248–254.

    Article  CAS  Google Scholar 

  16. Peng, L., & Shimizu, K. (2003). Global metabolic regulation analysis for Escherichia coli K12 based on protein expression by 2-dimensional electrophoresis and enzyme activity measurement. Applied Microbiology and Biotechnology, 61(2), 163–178.

    Article  CAS  Google Scholar 

  17. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using Real-time quantitative PCR and the 2− ΔΔCT method. Methods, 25(4), 402–408.

    Article  CAS  Google Scholar 

  18. Pan, W., Kang, Q., Wang, L., Bai, L., & Deng, Z. (2013). Asm8, a specific LAL-type activator of 3-amino-5-hydroxybenzoate biosynthesis in ansamitocin production. Science China. Life Sciences, 56(7), 601–608.

    Article  CAS  Google Scholar 

  19. Hobbs, G., Obanye, A. I., Petty, J., Mason, J. C., Barratt, E., Gardner, D. C., Flett, F., Smith, C. P., Broda, P., & Oliver, S. G. (1992). An integrated approach to studying regulation of production of the antibiotic methylenomycin by Streptomyces coelicolor A3(2). Journal of Bacteriology, 174(5), 1487–1494.

    CAS  Google Scholar 

  20. Ng, D., Chin, H. K., & Wong, V. V. (2009). Constitutive overexpression of asm2 and asm39 increases AP-3 production in the actinomycete Actinosynnema pretiosum. Journal of Industrial Microbiology and Biotechnology, 36(11), 1345–1351.

    Article  CAS  Google Scholar 

  21. Bandi, S., Kim, Y., Chang, Y. K., Shang, G., Yu, T. W., & Floss, H. G. (2006). Construction of asm2 deletion mutant of Actinosynnema pretiosum and medium optimization for ansamitocin P-3 production using statistical approach. Journal of Microbiology and Biotechnology , 16(9), 1338–1346.

    CAS  Google Scholar 

  22. Gao, Y., Fan, Y., Nambou, K., Wei, L., Liu, Z., Imanaka, T., & Hua, Q. (2014). Enhancement of ansamitocin P-3 production in Actinosynnema pretiosum by a synergistic effect of glycerol and glucose. Journal of Industrial Microbiology and Biotechnology, 41(1), 143–152.

    Article  CAS  Google Scholar 

  23. Jia, Y., & Zhong, J. J. (2011). Enhanced production of ansamitocin P-3 by addition of Mg2+ in fermentation of Actinosynnema pretiosum. Bioresource Technology , 102(21), 10147–10150.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was financially supported by the National Natural Science Foundation of China (Nos. 31200025 and 21406070), and Research Fund for the Doctoral Program of Higher Education of China (20130074110002) and partially supported by the Fundamental Research Funds for the Central Universities of China (WF1214045).

Author information

Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China

    Tinglan Li, Yuxiang Fan, Komi Nambou, Fengxian Hu, Tadayuki Imanaka, Liujing Wei & Qiang Hua

Authors
  1. Tinglan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuxiang Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Komi Nambou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fengxian Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tadayuki Imanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liujing Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qiang Hua
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liujing Wei.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Table S1

(DOC 117 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, T., Fan, Y., Nambou, K. et al. Improvement of Ansamitocin P-3 Production by Actinosynnema mirum with Fructose as the Sole Carbon Source. Appl Biochem Biotechnol 175, 2845–2856 (2015). https://doi.org/10.1007/s12010-014-1445-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-014-1445-6

Keywords

Search

Navigation