Skip to main content
SpringerLink
Log in

Daptomycin antibiotic production processes in fed-batch fermentation by Streptomyces roseosporus NRRL11379 with precursor effect and medium optimization

  • Original Paper
  • Published:
Bioprocess and Biosystems Engineering Aims and scope Submit manuscript

Abstract

Sodium decanoate was first found to be an effective precursor for synthesis of daptomycin from Streptomyces roseosporus NRRL11379 which was increased to 71.55-fold, compared with decanoic acid. The optimal flow rate of precursor was at 600 mg/(L day) after 48 h fermentation. From protein analysis via SDS-PAGE and identification of Tandem MS/MS afterwards, it deciphered that guanosine pentaphosphate synthetase, PNPase, tripeptidylamino peptidase primarily dealing with daptomycin synthesis. By applying Taguchi’s L16 in culture optimization, the best yield was obtained from the medium with 60 g/L dextrin, 10 g/L dextrose, 1.0 g/L molasses, and 8 g/L yeast extract, respectively. The fed-batch fermentation, applied with feedback control of dextrin, stimulated the production up to 812 mg/L at 288 h. To our best knowledge, the daptomycin production in this study is significantly higher than that in previous studies and can make it more widely used in pharmaceutical industry.

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. Olano C, Lombo F, Mendez C, Salas JA (2008) Improving production of bioactive secondary metabolites in actinomycetes by metabolic engineering. Metab Eng 10:281–292

    Article  CAS  Google Scholar 

  2. Mahlert C, Kopp F, Thirlway J, Micklefield J, Marahiel MA (2007) Stereospecific enzymatic transformation of r-ketoglutarate to (2S,3R)-3-methyl glutamate during acidic lipopeptide biosynthesis. JACS 129:12011–12018

    Article  CAS  Google Scholar 

  3. Doekel S, Gal MC, Gu JQ, Chu M, Baltz RH, Brian P (2008) Non-ribosomal peptide synthetase module fusions to produce derivatives of daptomycin in Streptomyces roseosporus. Microbiology 154:2872–2880

    Article  CAS  Google Scholar 

  4. Huang D, Jia X, Wen J, Wang G, Yu G, Caiyin Q, Chen Y (2011) Metabolic flux analysis and principal nodes identification for daptomycin production improvement by Streptomyces roseosporus. Appl Biochem Biotechnol 165:1725–1739

    Article  CAS  Google Scholar 

  5. Wang L, Zhao Y, Liu Q, Huang Y, Hu C, Liao G (2012) Improvement of A21978C production in Streptomyces roseosporus by reporter-guided rpsL mutation selection. J Appl Microbiol 112:1095–1101

    Article  CAS  Google Scholar 

  6. Hamill RL, Hoehn MM, Boeck LD, Carrell CB, Barnhart M, Debono M (1980) A21978C, a complex of new acidic peptide antibiotics: Fermentation, isolation and characterization studies. Program and Abstracts of 20th Interscience Conference on Antimicrobial Agents Chemotherapy 67:22–24

  7. Miao V, Coёffet-LeGal MF, Brian P, Brost R, Penn J, Whiting A, Martin S, Ford R, Parr I, Bouchard M, Silva CJ, Wrigley SK, Baltz RH (2005) Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the gene cluster and revision of peptide stereochemistry. Microbiology 151:1507–1523

    Article  CAS  Google Scholar 

  8. Nguyen KT, Kau D, Gu JQ, Brian P, Wrigley SK, Baltz RH, Miao V (2006) A glutamic acid 3-methyltransferase encoded by an accessory gene locus important for daptomycin biosynthesis in Streptomyces roseosporus. Mol Microbiol 6:1294–1307

    Article  CAS  Google Scholar 

  9. Arthur LB, Peter CF, Steven DB (2001) In vitro activities of daptomycin against 2,789 clinical isolates from 11 North American medical centers. Antimicrob Agents Chemother 45:1919–1922

    Article  Google Scholar 

  10. Tally FP, DeBruin MF (2000) Development of daptomycin for Gram-positive infections. J Antimicrob Chemother 46:523–526

    Article  CAS  Google Scholar 

  11. Mascio CT, Alder JD, Silverman JA (2007) Bactericidal action of daptomycin against stationary-phase and nondividing Staphylococcus aureus cells. Antimicrob Agents Chemother 51:4255–4260

    Article  CAS  Google Scholar 

  12. Wittmann M, Linne U, Pohlmann V, Marahiel MA (2008) Role of DptE and DptF in the lipidation reaction of daptomycin. FEBS 275:5343–5354

    Article  CAS  Google Scholar 

  13. Baltz RH, Miao V, Wrigley SK (2005) Natural products to drugs: daptomycin and related lipopeptide antibiotics. Nat Prod Rep 22:717–741

    Article  CAS  Google Scholar 

  14. Raja A, LaBonte J, Lebbos J, Kirkpatrick P (2003) Daptomycin. Nat Rev Durg Discover 2:943–944

    Article  CAS  Google Scholar 

  15. Yu G, Jia X, Wen J, Lu W, Wang G, Caiyin Q, Chen Y (2011) Strain Improvement of Streptomyces roseosporus for daptomycin production by rational screening of He–Ne laser and NTG induced mutants and kinetic modeling. Appl Biochem Biotechnol 163:729–743

    Article  CAS  Google Scholar 

  16. Yu G, Jia X, Wen J, Wang G, Chen Y (2011) Enhancement of daptomycin production in Streptomyces roseosporus LC-51 by manipulation of cofactors concentration in the fermentation culture. World J Microbiol Biotechnol 27:1859–1868

    Article  CAS  Google Scholar 

  17. Miller GL (1959) Use of dinitrosalicylic as reagent for the determination of reducing sugars. Anal Chem 31:426–428

    Article  CAS  Google Scholar 

  18. Thomas AH, Newland P (1987) Chromatographic methods for the analysis of vancomycin. J Chromatogr A 410:373–382

    Article  CAS  Google Scholar 

  19. Gallo G, Renzone G, Alduina R, Stegmann E, Weber T, Lantz AE et al (2010) Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina. Proteomics 10:1336–1358

    Article  CAS  Google Scholar 

  20. Holic R, Yazawa H, Kumagai H, Uemura H (2012) Engineered high content of ricinoleic acid in fission yeast Schizosaccharomyces pombe. Appl Microbiol Biotechnol 95:179–187

    Article  CAS  Google Scholar 

  21. Tomita M, Hayashi M, Awazu S (1995) Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine in Caco-2 cells. JPET 272:739–743

    CAS  Google Scholar 

  22. Boeck LD, Wetzel RW (1990) A54145, a new lipopeptide antibiotic complex: factor control through precursor directed biosynthesis. J Antibiot 43:607–615

    Article  CAS  Google Scholar 

  23. Lin JX, Bai L, Deng Z, Zhong JJ (2011) Enhanced production of ansamitocin P-3 by addition of iso-butanol in fermentation of Actinosynnema pretiosum. Bioresour Technol 102:1863–1868

    Article  CAS  Google Scholar 

  24. Bentley SD, Chater KF, Cerdeño-Tárraga AM, Challis GL, Thomson NR, James KD, Harris DE, Quail MA, Kieser H, Harper D, Bateman A, Brown S, Chandra G, Chen CW, Collins M, Cronin A, Fraser A, Goble A, Hidalgo J, Hornsby T, Howarth S, Huang CH, Kieser T, Larke L, Murphy L, Oliver K, O’Neil S, Rabbinowitsch E, Rajandream MA, Rutherford K, Rutter S, Seeger K, Saunders D, Sharp S, Squares R, Squares S, Taylor K, Warren T, Wietzorrek A, Woodward J, G. Barrell B, Parkhill J, Hopwood DA (2002) Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417:141–147

  25. Saudagar PS, Singhal RS (2007) A statistical approach using L(25) orthogonal array method to study fermentative production of clavulanic acid by Streptomyces clavuligerus MTCC 1142. Appl Biochem Biotechnol 136:345–359

    Article  CAS  Google Scholar 

  26. Wei ZH, Bai L, Deng Z, Zhong JJ (2012) Impact of nitrogen concentration on validamycin A production and related gene transcription in fermentation of Streptomyces hygroscopicus 5008. Bioprocess Biosyst Eng 35:1201–1208

    Article  CAS  Google Scholar 

  27. Ezaki M, Iwami M, Yamashita M, Komori T, Umehara K, Imanaka H (1992) Biphenomycin A production by a mixed culture. Appl Environ Microbiol 58:3879–3882

    CAS  Google Scholar 

  28. Saudagar PS, Singhal RS (2007) Optimization of nutritional requirements and feeding strategies for clavulanic acid production by Streptomyces clavuligerus. Bioresour Technol 98:2010–2017

    Article  CAS  Google Scholar 

  29. Chen GQ, Lu FP, Du LX (2008) Natamycin production by Streptomyces gilvosporeus based on statistical optimization. J Agric Food Chem 56:5057–5061

    Article  CAS  Google Scholar 

  30. Müller JM, Risse JM, Jussen D, Flaschel E (2013) Development of fed-batch strategies for the production of streptavidin by Streptomyces avidinii based on power input and oxygen supply studies. J Biotechnol 163:325–332

    Article  CAS  Google Scholar 

  31. Zhu X, Zhang W, Chen X, Wu H, Duan Y, Xu Z (2010) Generation of high rapamycin producing strain via rational metabolic pathway-based mutagenesis and further titer improvement with fed-batch bioprocess optimization. Biotechnol Bioeng 107:506–515

    Article  CAS  Google Scholar 

  32. Lu W, Fan J, Wen J, Xia Z, Caiyin Q (2011) Kinetic analysis and modeling of daptomycin batch fermentation by Streptomyces roseosporus. Appl Biochem Biotechnol 163:453–462

    Article  CAS  Google Scholar 

  33. Penn J, Li X, Whiting A, Latif M, Gibson T, Silva CJ, Brian P, Davies J, Miao V, Wrigley SK, Baltz RH (2006) Heterologous production of daptomycin in Streptomyces lividans. J Ind Microbiol Biotechnol 33:121–128

    Article  CAS  Google Scholar 

  34. Kaminskyj SG, Dahms TE (2008) High spatial resolution surface imaging and analysis of fungal cells using SEM and AFM. Micron 39:349–361

    Article  CAS  Google Scholar 

  35. Castillo U, Myers S, Browne L, Strobel G, Hess WM, Hanks J, Reay D (2005) Scanning electron microscopy of some endophytic streptomycetes in snakevine–Kennedia nigricans. Scanning 27:305–311

    Article  Google Scholar 

  36. Giudici R, Pamboukian CR, Facciotti MC (2004) Morphologically structured model for antitumoral retamycin production during batch and fed-batch cultivations of Streptomyces olindensis. Biotechnol Bioeng 86:414–424

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the financial support by the Fundamental Research Funds for the Central Universities (2011121017), the Chinese National Natural Science Foundation (21206141) and the Fujian Provincial Department of Science and Technology (2012I0009).

Author information

Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China

    I-Son Ng, Chiming Ye, Zhixiang Zhang, Yinghua Lu & Keju Jing

  2. The Key Laboratory for Synthetic Biotechnology of Xiamen City, Xiamen University, Xiamen, 361005, China

    I-Son Ng, Yinghua Lu & Keju Jing

Authors
  1. I-Son Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chiming Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhixiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yinghua Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Keju Jing
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I-Son Ng.

Additional information

C. Ye and Z. Zhang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ng, IS., Ye, C., Zhang, Z. et al. Daptomycin antibiotic production processes in fed-batch fermentation by Streptomyces roseosporus NRRL11379 with precursor effect and medium optimization. Bioprocess Biosyst Eng 37, 415–423 (2014). https://doi.org/10.1007/s00449-013-1007-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00449-013-1007-2

Keywords

Search

Navigation