Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Biosynthesis of Novel Glucosides Geldanamycin Analogs by Enzymatic Synthesis

  • Huo, Qiang (Faculty of Pharmacy, Bengbu Medical College) ;
  • Li, Hong-Mei (Faculty of Pharmacy, Bengbu Medical College) ;
  • Lee, Jae Kyoung (Chemical Biology Research Center, KRIBB) ;
  • Li, Jing (Faculty of Pharmacy, Bengbu Medical College) ;
  • Ma, Tao (Faculty of Pharmacy, Bengbu Medical College) ;
  • Zhang, Xinyu (Faculty of Pharmacy, Bengbu Medical College) ;
  • Dai, Yiqun (Faculty of Pharmacy, Bengbu Medical College) ;
  • Hong, Young-Soo (Chemical Biology Research Center, KRIBB) ;
  • Wu, Cheng-Zhu (Faculty of Pharmacy, Bengbu Medical College)
  • Received : 2015.08.24
  • Accepted : 2015.10.09
  • Published : 2016.01.28
Download PDF
⟨ Previous Next ⟩

Abstract

Two new glucosides (1 and 2) of geldanamycin (GA) analogs were obtained from in vitro glycosylation by UDP-glycosyltransferase (YjiC). Based on spectroscopic (HR-ESI-MS, 1D, and 2D-NMR) analyses, the glucosides were elucidated as 4,5-dihydro-7-O-descarbamoyl-7-hydroxyl GA-7-O-β-D-glucoside (1) and ACDL3172-18-O-β-D-glucoside (2). Furthermore, the water solubility of compounds 1 and 2 was about 215.2 and 90.7 times higher respectively, than that of the substrates. Among compounds 1-4, only 3 showed weak antiproliferative activity against four human tumor cell lines: MDA-MB-231, SMMC7721, HepG2, and SW480 (IC50: 13.6, 15.1, 31.8, and 22.7 μM, respectively).

Keywords

References

  1. Cheng H, Cao X, Xian M, Fang L, Cai TB, Ji JJ, et al. 2005. Synthesis and enzyme-specific activation of carbohydrategeldanamycin conjugates with potent anticancer activity. J. Med. Chem. 48: 645-652. https://doi.org/10.1021/jm049693a
  2. DeBoer C, Meulman PA, Wnuk RJ, Peterson DH. 1970. Geldanamycin, a new antibiotic. J. Antibiot. (Tokyo) 23: 442-447. https://doi.org/10.7164/antibiotics.23.442
  3. Dhakal D, Le TT, Pandey RP, Jha AK, Gurung R, Parajuli P, et al. 2015. Enhanced production of nargenicin A1 and generation of novel glycoslated derivatives. Appl. Biochem. Biotechnol. 175: 2934-2949. https://doi.org/10.1007/s12010-014-1472-3
  4. Elshahawi SI, Shaaban KA, Kharel MK, Thorson JS. 2015. A comprehensive review of glycosylated bacterial natural products. Chem. Soc. Rev. DOI: 10.1039/c4cs00426d.
  5. Fukuyo Y, Hunt CR, Horikoshi N. 2009. Geldanamycin and its anti-cancer activities. Cancer Lett. 290: 24-35. https://doi.org/10.1016/j.canlet.2009.07.010
  6. Hong YS, Lee D, Kim W, Jeong JK, Kim CG, Sohng JK, et al. 2004. Inactivation of the carbamoyltransferase gene refines post-polyketide synthase modification steps in the biosynthesis of the antitumor agent geldanamycin. J. Am. Chem. Soc. 126: 11142-11143. https://doi.org/10.1021/ja047769m
  7. Kim W, Lee D, Hong SS, Na Z, Shin JC, Roh SH, et al. 2009. Rational biosynthetic engineering for optimization of geldanamycin analogues. ChemBioChem 10: 1243-1251. https://doi.org/10.1002/cbic.200800763
  8. Kim W, Lee JS, Lee D, Cai XF, Shin JC, Lee K, et al. 2007. Mutasynthesis of geldanamycin by the disruption of gene producing starter unit: generation of structural diversity at the benzoquinone ring. ChemBioChem 8: 1491-1494. https://doi.org/10.1002/cbic.200700196
  9. Lee D, Lee K, Cai XF, Dat NT, Boovanahalli SK, Lee M, et al. 2006. Biosynthesis of the heat-shock protein 90 inhibitor geldanamycin: new insight into the formation of the benzoquinone moiety. ChemBioChem 7: 246-248. https://doi.org/10.1002/cbic.200500441
  10. Lee K, Ryu JS, Jin Y, Kim W, Kaur N, Chung SJ, et al. 2008. Synthesis and anticancer activity of geldanamycin derivatives derived from biosynthetically generated mebabolites. Org. Biomol. Chem. 6: 340-348. https://doi.org/10.1039/B713407J
  11. Pandey RP, Gurung RB, Parajuli PP, Koirala N, Tuoi LT, Sohng JK. 2014. Assessing acceptor substrate promiscuity of YjiC-mediated glycosylation toward flavonoids. Carbohydr. Res. 393: 26-31. https://doi.org/10.1016/j.carres.2014.03.011
  12. Pandey RP, Parajuli P, Shin JY, Lee J, Lee S, Hong YS, et al. 2014. Enzymatic biosynthesis of novel resveratrol glucoside and glycoside derivatives. Appl. Environ. Microbiol. 80: 7235-7243. https://doi.org/10.1128/AEM.02076-14
  13. Schulte TW, Neckers LM. 1998. The benzoquinone ansamycin 17-allylamino-17-demethoxy geldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother. Pharmacol. 42: 273-279. https://doi.org/10.1007/s002800050817
  14. Singh S, Phillips GJ, Thorson JS. 2012. The structural biology of enzymes involved in natural product glycosylation. Nat. Prod. Rep. 29: 1201-1237. https://doi.org/10.1039/c2np20039b
  15. Solárová Z, Mojžiš J, Solár P. 2015. Hsp90 inhibitor as a sensitizer of cancer cells to different therapies. Int. J. Oncol. 46: 907-926.
  16. Supko JG, Hickman RL, Grever MR, Malspeis L. 1995. Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother. Pharmacol. 36: 305-315. https://doi.org/10.1007/BF00689048
  17. Whitesell L, Mimnaugh EG, Costa BD, Myers CE, Neckers LM. 1994. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc. Natl. Acad. Sci. USA 91: 8324-8328. https://doi.org/10.1073/pnas.91.18.8324
  18. Wu CZ, Jang JH, Woo MH, Ahn JS, Kim JS, Hong YS. 2012. Enzymatic glycosylation of non benzoquinone geldanamycin analogs via Bacillus UDP-glycosyltransferase. Appl. Environ. Microbiol. 78: 7680-7686. https://doi.org/10.1128/AEM.02004-12
  19. Yang L, Wang Z, Lei H, Chen R, Wang X, Peng Y, Dai J. 2014. Neuroprotective glucosides of magnolol and honokiol from microbial-specific glycosylation. Tetrahedron 70: 8244-8251. https://doi.org/10.1016/j.tet.2014.09.033

Cited by

  1. Fermentative Production of Phenolic Glucosides by Escherichia coli with an Engineered Glucosyltransferase from Rhodiola sachalinensis vol.65, pp.23, 2017, https://doi.org/10.1021/acs.jafc.7b00981
  2. Enzyme-Catalyzed Glycosylation of Curcumin and Its Analogues by Glycosyltransferases from Bacillus subtilis ATCC 6633 vol.9, pp.9, 2016, https://doi.org/10.3390/catal9090734