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Enhancement of ε-poly-l-lysine production coupled with precursor l-lysine feeding in glucose–glycerol co-fermentation by Streptomyces sp. M-Z18

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Abstract

ε-Poly-l-lysine (ε-PL), one of the only two homo-poly amino acids known in nature, is used as a preservative. In this study, strategies of feeding precursor l-lysine into 5 L laboratory scale fermenters, including optimization of l-lysine concentration and time, was investigated to optimize the production of ε-PL by Streptomyces sp. M-Z18. The optimized strategy was then used in ε-PL fed-batch fermentation in which glucose and glycerol served as mixed carbon sources. In this way, a novel ε-PL production strategy involving precursor l-lysine coupled with glucose–glycerol co-fermentation was developed. Under optimal conditions, ε-PL production reached 37.6 g/l, which was 6.2 % greater than in a previous study in which glucose and glycerol co-fermentation was performed without added l-lysine (35.14 g/l). To the best of our knowledge, this is the first report of the enhancement of ε-PL production through l-lysine feeding to evaluate the use of fermenters. Meanwhile, the role of l-lysine in the promotion of ε-PL production, participating ε-PL synthesis as a whole, was first determined using the l-[U–13C] lysine labeling method. It has been suggested that the bottleneck of ε-PL synthesis in Streptomyces sp. M-Z18 is in the biosynthesis of precursor l-lysine. The information obtained in the present work may facilitate strain improvement and efficient large-scale ε-PL production.

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References

  1. Shima S, Sakai H (1977) Polylysine produced by Streptomyces. Agric Biol Chem 41:1807–1809

    Article  CAS  Google Scholar 

  2. Saimura M, Takehara M, Mizukami S, Kataoka K, Hirohara H (2008) Biosynthesis of nearly monodispersed poly(ε-l-lysine) in Streptomyces species. Biotechnol Lett 30:377–385

    Article  CAS  Google Scholar 

  3. Hiraki J, Masakazu H, Hiroshi M, Yoshikazu I (1998) Improved ε-poly-l-lysine production of an S-(2-aminoethyl)-l-cysteine resistant mutant of Streptomyces albulus. Seibutu Kougaku Kaishi 76:487–493

    CAS  Google Scholar 

  4. Shih IL, Shen MH (2006) Application of response surface methodology to optimize production of poly-ε-lysine by Streptomyces albulus IFO 14147. Enzyme Microb Technol 39:15–21

    Article  CAS  Google Scholar 

  5. Kobayashi K, Nishikawa M (2007) Promotion of ε-poly-l-lysine production by iron in Kitasatospora Kifunense. World J Microbiol Biotechnol 23:1033–1036

    Article  CAS  Google Scholar 

  6. Kahar P, Iwata T, Hiraki J, Park EY, Okabe M (2001) Enhancement of ε-polylysine production by Streptomyces albulus strain 410 using pH control. J Biosci Bioeng 91:190–194

    CAS  Google Scholar 

  7. Hiraki J, Suzuki E (1999) Process for producing ε-poly-l-lysine with immobilized Streptomyces albulus. US Patent 5900363

  8. Liu S, Wu Q, Zhang J, Mo S (2011) Production of ε-poly-l-lysine by Streptomyces sp. using resin-based, in situ product removal. Biotechnol Lett 33:1581–1585

    Article  CAS  Google Scholar 

  9. Chen XS, Li S, Liao LJ, Ren XD, Li F, Tang L, Zhang JH, Mao ZG (2011) Production of ε-poly-l-lysine using a novel two-stage pH control strategy by Streptomyces sp. M-Z18 from glycerol. Bioprocess Biosyst Eng 34:561–567

    Article  CAS  Google Scholar 

  10. Chen XS, Ren XD, Dong N, Li S, Li F, Zhao FL, Tang L, Zhang JH, Mao ZG (2012) Culture medium containing glucose and glycerol as a mixed carbon source improves ε-poly-l-lysine production by Streptomyces sp. M-Z18. Bioprocess Biosyst Eng 35:469–475

    Article  CAS  Google Scholar 

  11. Bankar SB, Singhal RS (2011) Improved poly-ε-lysine biosynthesis using Streptomyces noursei NRRL 5126 by controlling dissolved oxygen during fermentation. J Microbiol Biotechnol 21:652–658

    CAS  Google Scholar 

  12. Mao XZ, Wang F, Zhang JG, Chen S, Deng ZX, Shen YL, Wei DZ (2009) The pH shift and precursor feeding strategy in a low-toxicity FR-008/candicidin derivative CS103 fermentation bioprocess by a mutant of Streptomyces sp. FR-008. Appl Biochem Biotechnol 159:673–686

    Article  CAS  Google Scholar 

  13. Zhou WW, Ma B, Tang YJ, Zhong JJ, Zheng XD (2012) Enhancement of validamycin A production by addition of ethanol in fermentation of Streptomyces hygroscopicus 5008. Bioresour Technol 114:616–621

    Article  CAS  Google Scholar 

  14. Chen XL, Xu YH, Zheng YG, Shen YC (2010) Improvement of tautomycin production in Streptomyces spiroverticillatus by feeding glucose and maleic anhydride. Biotechnol Bioprocess Eng 15:969–974

    Article  CAS  Google Scholar 

  15. Shima S, Oshima S, Sakai H (1983) Biosynthesis of ε-poly-l-lysine by washed mycelium of Streptomyces albulus no. 346. Nippon Nogeikagaku Kaishi 57:221–226

    Article  CAS  Google Scholar 

  16. Kawai T, Kubota T, Hiraki J, Izumi Y (2003) Biosynthesis of ε-poly-l-lysine in a cell-free system of Streptomyces albulus. Biochem Biophys Res Commun 311:635–640

    Article  CAS  Google Scholar 

  17. Yamanaka K, Maruyama C, Takagi H, Hamano Y (2008) ε-Poly-l-lysine dispersity is controlled by a highly unusual nonribosomal peptide synthetase. Nat Chem Biol 4:766–772

    Article  CAS  Google Scholar 

  18. Hirohara H, Takehara M, Saimura M, Masayuki A, Miyamoto M (2006) Biosynthesis of poly(ε-l-lysine)s in two newly isolated strains of Streptomyces sp. Appl Microbiol Biotechnol 73:321–331

    Article  CAS  Google Scholar 

  19. Bankar SB, Singhal RS (2011) Metabolic precursors enhance the production of poly-ε-lysine by Streptomyces noursei NRRL 5126. Eng Life Sci 11:253–258

    Article  CAS  Google Scholar 

  20. Jia SR, Mo ZW, Tan ZL, Wang GL, Fan BQ, Wang T, Li L, Zhou B (2010) A new method for enhancing ε-poly-l-lysine production. China patent CN101671703A

  21. Zhang Y, Feng XH, Xu H, Yao Z, Ouyang PK (2010) ε-Poly-l-lysine production by immobilized cells of Kitasatospora sp. MY 5–36 in repeated fed-batch cultures. Bioresour Technol 101:5523–5527

    Article  CAS  Google Scholar 

  22. Itzhaki RF (1972) Colorimetric method for estimating polylysine and polyarginine. Anal Biochem 50:569–574

    Article  CAS  Google Scholar 

  23. Rahulan R, Dhar KS, Madhavan Nampoothiri K, Pandey A (2011) Production of leucine amino peptidase in lab scale bioreactors using Streptomyces gedanensis. Bioresour Technol 102:8171–8178

    Article  CAS  Google Scholar 

  24. Hamano Y, Nicchu I, Shimizu T, Onji Y, Hiraki J, Takagi H (2007) epsilon-Poly-l-lysine producer, Streptomyces albulus, has feedback-inhibition resistant aspartokinase. Appl Microbiol Biotechnol 76:873–882

    Article  CAS  Google Scholar 

  25. Anne-Marie C, Gross RA (1995) Investigation by NMR of metabolic routes to bacterial γ-poly(glutamic acid) using 13C-labeled citrate and glutamate as media carbon sources. Can J Microbiol 41:902–909

    Article  Google Scholar 

  26. Maeda S, Kunimoto KK, Sasaki C, Kuwae A, Hanai K (2003) Characterization of microbial poly (ε-l-lysine) by FT-IR, Raman and solid state 13C NMR spectroscopies. J Mol Struct 655:149–155

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the Jiangsu Key Project of Scientific and Technical Supporting Program (BE2012616), the Fundamental Research Funds for the Central Universities (JUSRP11217), the Wuxi Science and Technology Support Program (CYE21N1107), the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the 111 Project (111-2-06).

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Correspondence to Zhong-Gui Mao.

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Chen, XS., Ren, XD., Zeng, X. et al. Enhancement of ε-poly-l-lysine production coupled with precursor l-lysine feeding in glucose–glycerol co-fermentation by Streptomyces sp. M-Z18. Bioprocess Biosyst Eng 36, 1843–1849 (2013). https://doi.org/10.1007/s00449-013-0958-7

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