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논문 상세정보


Abstract Cyclosporins are a family of clinically-important immunosuppressive cyclic peptides produced by Tolypocladium inflatum. The structural modification of cyclosporins via hydroxylation at various positions of N-methyl leucines in cyclosporin A leads to a dramatic change of their bioactive spectra. Among over 100 soil actinomycetes screened, two actinomycetes species, Sebekia benihana and Pseudonocardia autotrophica, were identified to contain superior cyclosporin A hydroxylation activities. A HPLC-based cyclosporin A hydroxylation assay revealed that each strain possesses distinctive hydroxylation specificity and regiospecificity; mono-hydroxylation at the 4th N-methyl leucine of cyclosporin A by S. benihana, and di-hydroxylations at both 4th and 9th N-methyl leucines of cyclosporin A by P. autotrophica. The conversion yields for cyclosporin A hydroxylation by both S. benihana and P. autotrophica were significantly improved from less than 10% and 18% up to 58% and 45%, respectively, in the optimized culture containing molybdenum with 0.05 g/l of cyclosporin A concentration. An ancymidol-specific inhibition of cyclosporin hydroxylation also suggested that the regiospecific cyclosporin hydroxylation might be catalyzed by a putative cytochrome P450 mono-oxygenase enzyme.

참고문헌 (22)

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이 논문을 인용한 문헌 (9)

  1. 2006. "" Journal of microbiology and biotechnology, 16(2): 295~298 
  2. 2006. "" Journal of microbiology and biotechnology, 16(7): 1032~1040 
  3. 2006. "" Journal of microbiology and biotechnology, 16(9): 1477~1480 
  4. 2007. "" Journal of microbiology and biotechnology, 17(12): 1930~1936 
  5. 2007. "" Journal of microbiology and biotechnology, 17(9): 1538~1545 
  6. 2007. "" Journal of microbiology and biotechnology, 17(3): 403~407 
  7. 2008. "" Journal of microbiology and biotechnology, 18(5): 913~917 
  8. Kim, Hyun-Bum ; Lee, Mi-Jin ; Han, Kyu-Boem ; Kim, Eung-Soo 2010. "Improvement of Cyclosporin A Hydroxylation in Sebekia benihana by Conjugational Transfer of Streptomyces coelicolor SCO4967, a Secondary Metabolite Regulatory Gene" 한국미생물·생명공학회지 = Korean journal of microbiology and biotechnology, 38(4): 475~480 
  9. 2011. "" Journal of microbiology and biotechnology, 21(1): 14~19 


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