한국미생물·생명공학회지 (Microbiology and Biotechnology Letters)

  • 제48권3호
  • /
  • Pages.296-302
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  • 2020
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  • 1598-642X(pISSN)
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  • 2234-7305(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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Effects of Glycerol and Shikimic Acid on Rapamycin Production in Streptomyces rapamycinicus

  • La, Huyen Thi Huong (VNU Institute of Microbiology and Biotechnology, Vietnam National University) ;
  • Nguyen, Thao Kim Nu (VNU Institute of Microbiology and Biotechnology, Vietnam National University) ;
  • Dinh, Hang Thuy (VNU Institute of Microbiology and Biotechnology, Vietnam National University) ;
  • Nguyen, Quyen Minh Huynh (VNU Institute of Microbiology and Biotechnology, Vietnam National University) ;
  • Nguyen, Minh Hong (VNU Institute of Microbiology and Biotechnology, Vietnam National University)
  • 투고 : 2020.01.03
  • 심사 : 2020.03.05
  • 발행 : 2020.09.28
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초록

Rapamycin, derived from Streptomyces rapamycinicus, is an important bioactive compound having a therapeutic value in managing Parkinson's disease, rheumatoid arthritis, cancer, and AIDS. Because of its pharmaceutical activity, studies over the past decade have focused on the biosynthesis of rapamycin to enhance its yield. In this study, the effect of rapG on rapamycin production was investigated. The rapG expression vector was constructed by utilizing the integration vector pSET152 under the control of the erythromycin resistance gene (ermE⁎), a strong constitutive promoter. The rapamycin yield of wild type (WT) and WT/rapG overexpression mutant strains, under fermentation conditions, was analyzed by high-performance liquid chromatography (HPLC). Our results revealed that overexpression of rapG increased rapamycin production by approximately 4.9-fold (211.4 mg/l) in MD1 containing 15 g/l of glycerol, compared to that of the WT strain. It was also found that Illicium verum powder (10 g/l), containing shikimic acid, enhanced rapamycin production in both WT and WT/rapG strains. Moreover, the amount of rapamycin produced by the WT/rapG strain was statistically higher than that produced by the WT strain. In conclusion, the addition 15 g/l glycerol and 15 g/l I. verum powder produced the optimal conditions for rapamycin production by WT and WT/rapG strains.

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참고문헌

  1. Vezina C, Kudelski A, Sehgal SN. 1975. Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J. Antibiot. 28: 721-726. https://doi.org/10.7164/antibiotics.28.721
  2. Park SR, Yoo YJ, Ban YH, Yoon YJ. 2010. Biosynthesis of rapamycin and its regulation: past achievements and recent progress. J. Antibiot. 63: 434-441. https://doi.org/10.1038/ja.2010.71
  3. Tain LS, Mortiboys H, Tao RN, Ziviani E, Bandmann O, Whitworth AJ. 2009. Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat. Neurosci. 12: 1129-1135. https://doi.org/10.1038/nn.2372
  4. Shao P, Ma L, Ren Y, Liu H. 2017. Modulation of the immune response in rheumatoid arthritis with strategically released rapamycin. Mol. Med. Rep. 16: 5257-5262. https://doi.org/10.3892/mmr.2017.7285
  5. Zou CY, Smith KD, Zhu QS, Liu J, McCutcheon IE, Slopis JM, et al. 2009. Dual targeting of AKT and mammalian target of rapamycin: a potential therapeutic approach for malignant peripheral nerve sheath tumor. Mol. Cancer Ther. 8: 1157-1168. https://doi.org/10.1158/1535-7163.MCT-08-1008
  6. Nicoletti F, Lapenta C, Donati S, Spada M, Ranazzi A, Cacopardo B, et al. 2009. Inhibition of human immunodeficiency virus (HIV-1) infection in human peripheral blood leucocytes-SCID reconstituted mice by rapamycin. Clin. Exp. Immunol. 155: 28-34. https://doi.org/10.1111/j.1365-2249.2008.03780.x
  7. Molnar I, Aparicio JF, Haydock SF, Khaw LE, Schwecke T, Konig A, et al. 1996. Organisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of genes flanking the polyketide synthase. Gene. 169: 1-7. https://doi.org/10.1016/0378-1119(95)00799-7
  8. Kuscer E, Coates N, Challis I, Gregory M, Wilkinson B, Sheridan R, et al. 2007. Roles of rapH and rapG in positive regulation of rapamycin biosynthesis in Streptomyces hygroscopicus. J. Bacteriol. 189: 4756-4763. https://doi.org/10.1128/JB.00129-07
  9. Kim YH, Park BS, Bhatia SK, Seo HM, Jeon JM, Kim HJ, et al. 2014. Production of rapamycin in Streptomyces hygroscopicus from glycerol-based media optimized by systemic methodology. J. Microbiol. Biotechnol. 24: 1319-1326. https://doi.org/10.4014/jmb.1403.03024
  10. Zhu X, Zhang W, Chen X, Wu H, Duan Y, Xu Z. 2010. Generation of high rapamycin producing strain via rational metabolic pathwaybased mutagenesis and further titer improvement with fedbatch bioprocess optimization. Biotechnol. Bioeng. 107: 506-515. https://doi.org/10.1002/bit.22819
  11. Paiva NL, Roberts MF, Demain AL. 1993. The cyclohexane moiety of rapamycin is derived from shikimic acid in Streptomyces hygroscopicus. J. Ind. Microbiol. Biotechnol. 12: 423-428.
  12. Fang A, Demain AL. 1995. Exogenous shikimic acid stimulates rapamycin biosynthesis in Streptomyces hygroscopicus. Folia Microbiol. (Praha) 40: 607-610. https://doi.org/10.1007/BF02818516
  13. Lee MS, Kojima I, Demain AL. 1997. Effect of nitrogen source on biosynthesis of rapamycin by Streptomyces hygroscopicus. J. Ind. Microbiol. Biotechnol. 19: 83-86. https://doi.org/10.1038/sj.jim.2900434
  14. Yen HW, Hsiao HP. 2013. Effects of dissolved oxygen level on rapamycin production by pellet-form of Streptomyces hygroscopicus. J. Biosci. Bioeng. 116: 366-370. https://doi.org/10.1016/j.jbiosc.2013.03.011
  15. Yen H-W, Hsiao H-P, Chen L-J. 2013. The enhancement of rapamycin production using Streptomyces hygroscopicus through a simple pHshifted control. J. Taiwan Inst. Chem. E. 44: 743-747. https://doi.org/10.1016/j.jtice.2013.01.025
  16. Hanahan D. 1983. Studies on transformation of Escherichia coli with plasmids. J. Mol. Biol. 166: 557-580. https://doi.org/10.1016/S0022-2836(83)80284-8
  17. Kurniawan YN, Kitani S, Iida A, Maeda A, Lycklama a Nijeholt J, Lee YJ, et al. 2016. Regulation of production of the blue pigment indigoidine by the pseudo gamma-butyrolactone receptor FarR2 in Streptomyces lavendulae FRI-5. J. Biosci. Bioeng. 121: 372-379. https://doi.org/10.1016/j.jbiosc.2015.08.013
  18. Dai D, Pu T, Liang J, Wang Z, Tang A. 2018. Regulation of dndB gene expression in Streptomyces lividans. Front. Microbiol. 9: 2387. https://doi.org/10.3389/fmicb.2018.02387
  19. Sallama LAR, El-Refaia AF, Osmanb ME, Hamdya AA, Ahmeda EM, Mohameda MA. 2010. Some physiological factors affecting rapamycin production by Streptomyces hygroscopicus ATCC 29253. Am. J. Sci. 6: 188-194.
  20. More AS, Gadalkar S, Rathod VK. 2017. Extraction of rapamycin (sirolimus) from Streptomyces rapamycinicus using ultrasound. Prep. Biochem. Biotechnol. 47: 627-632. https://doi.org/10.1080/10826068.2017.1303609
  21. Dutta S, Basak B, Bhunia B, Chakraborty S, Dey A. 2014. Kinetics of rapamycin production by Streptomyces hygroscopicus MTCC 4003. 3 Biotech. 4: 523-531. https://doi.org/10.1007/s13205-013-0189-2
  22. Ohira H, Torii N, Aida TM, Watanabe M, Smith RL. 2009. Rapid separation of shikimic acid from Chinese star anise (Illicium verum Hook. f.) with hot water extraction. Sep. Purif. Technol. 69: 102-108. https://doi.org/10.1016/j.seppur.2009.07.005
  23. Bierman M, Logan R, O'Brien K, Seno ET, Rao RN, Schoner BE. 1992. Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene 116: 43-49. https://doi.org/10.1016/0378-1119(92)90627-2