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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 한국미생물생명공학회 Journal of Microbiology and Biotechnology Journal of Microbiology and Biotechnology 제25권 제10호
- 발행연도
- 2015.1
- 수록면
- 1,634 - 1,639 (6page)
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Cytochrome P450 hydroxylase (CYP) in actinomycetes plays an important role in the biosynthesis and bioconversion of various secondary metabolites. Two unique CYPs named CYP-sb21 and CYP-pa1, which were identified from Sebekia benihana and Pseudonocardia autotrophica, respectively, were proven to transfer a hydroxyl group at the 4th or 9th N-methyl leucine position of immunosuppressive agent cyclosporin A (CsA). Interestingly, these two homologous CYPs showed different CsA regio-selectivities. CYP-sb21 exhibited preferential hydroxylation activity at the 4th position over the 9th position, whereas CYP-pa1 showed the opposite preference. To narrow down the CYP domain critical for CsA regio-selectivity, each CYP was divided into four domains, and each domain was swapped with its counterpart from the other CYP. A total of 18 hybrid CYPs were then individually tested for CsA regioselectivity. Although most of the hybrid CYPs failed to exhibit a significant change in regioselectivity in the context of CsA hydroxylation, hybrid CYP-pa1 swapped with the second domain of CYP-sb21 showed a higher preference for the 9th position. Moreover, hybrid CYPsb21 containing seven amino acids from the 2nd domain of CYP-pa1 showed higher preference for the 4th position. These results imply that the 2nd domain of CsA-specific CYP plays a critical role in CsA regio-selectivity, thereby setting the stage for biotechnological application of CsA regio-selective hydroxylation.
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참고문헌 (14)
참고문헌 신청
Ban JG / 2014 / A novel regiospecific cyclosporin hydroxylase gene revealed through the genome mining of Pseudonocardia autotrophica / J. Ind. Microbiol. Biotechnol 41 : 879
Behal V. / 2000 / Bioactive products from Streptomyces / Adv. Appl. Microbiol 47 : 113 ~ 156
Choi SU / 2004 / Intergeneric conjugal transfer of plasmid DNA from Escherichia coli to Kitasatospora setae, a bafilomycin B1 producer / Arch. Microbiol 181 : 294 ~ 298
Coghlan VM / 1991 / Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc / J. Biol. Chem 266 : 18606 ~ 18612
Delort AM / 1988 / Microbial conversion of nigericin in three successive steps, by Sebekia benihana / J. Antibiot. (Tokyo) 41 : 916 ~ 924
Behal V. / 2000 / Bioactive products from Streptomyces / Adv. Appl. Microbiol 47 : 113 ~ 156
Choi SU / 2004 / Intergeneric conjugal transfer of plasmid DNA from Escherichia coli to Kitasatospora setae, a bafilomycin B1 producer / Arch. Microbiol 181 : 294 ~ 298
Coghlan VM / 1991 / Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc / J. Biol. Chem 266 : 18606 ~ 18612
Delort AM / 1988 / Microbial conversion of nigericin in three successive steps, by Sebekia benihana / J. Antibiot. (Tokyo) 41 : 916 ~ 924
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