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Characterization and Culture Optimization of Regiospecific Cyclosporin Hydroxylation in Rare Actinomycetes Species

Journal of microbiology and biotechnology v.15 no.1 , 2005년, pp.188 - 191  
PARK, NAM-SIL (Department of Biotechnology, Inha University ) ;  MYEONG, JI-SEON ( Department of Biotechnology, Inha University ) ;  PARK, HYUN-JOO ( Song Won Envichem Inc. ) ;  HAN, KYU-BOEM ( Hanson Biotech Co., Ltd. 201 IACRI, Han Nam University ) ;  KIM, SANG-NYUN ( LG Household and HealthCare, R&D Park ) ;  KIM, EUNG-SOO ( Department of Biotechnology, Inha University)
Abstract

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.

주제어

#Cyclosporin   #hydroxylation   #actinomycetes   #bioconversion  

저자의 다른 논문

PARK, NAM-SIL(2) MYEONG, JI-SEON(3) KIM, EUNG-SOO(33)

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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