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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 한국미생물생명공학회 Journal of Microbiology and Biotechnology Journal of Microbiology and Biotechnology 제27권 제5호
- 발행연도
- 2017.1
- 수록면
- 956 - 964 (9page)
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Compactin and pravastatin are competitive cholesterol biosynthesis inhibitors of 3-hydroxy-3- methylglutaryl-CoA reductase and belong to the statin drugs; however, the latter shows superior pharmacokinetic characteristics. Previously, we reported that the bacterial P450, CYP105D7, from Streptomyces avermitilis can catalyze the hydroxylation of 1-deoxypentalenic acid, diclofenac, and naringenin. Here, we demonstrate that CYP105D7 could also catalyze compactin hydroxylation in vitro. In the presence of both bacterial and cyanobacterial redox partner systems with an NADPH regeneration system, the reaction produced two hydroxylated products, including pravastatin (hydroxylated at the C6 position). The steadystate kinetic parameters were measured using the redox partners of putidaredoxin and its reductase. The Km and kcat values for compactin were 39.1 ± 8.8 μM and 1.12 ± 0.09 min-1, respectively. The kcat/Km value for compactin (0.029 min-1·μM-1) was lower than that for diclofenac (0.114 min-1·μM-1). Spectroscopic analysis showed that CYP105D7 binds to compactin with a Kd value of 17.5 ± 3.6 μM. Molecular docking analysis was performed to build a possible binding model of compactin. Comparisons of different substrates with CYP105D7 were conclusively illustrated for the first time.
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참고문헌 (22)
참고문헌 신청
Bernhardt R. / 2006 / Cytochromes P450 as versatile biocatalysts / J. Biotechnol 124 : 128 ~ 145
Chun Y-J / 2007 / Electron transport pathway for a Streptomyces cytochrome P450: cytochrome P450 105D5-catalyzed fatty acid hydroxylation in Streptomyces coelicolor A3(2) /
Endo A / 1976 / ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinum / J. Antibiot 29 : 1346 ~ 1348
Fasan R. / 2012 / Tuning P450 enzymes as oxidation catalysts / ACS Catal 2 : 647 ~ 666
Guengerich FP. / 2002 / Rate-limiting steps in cytochrome P450 catalysis / Biol. Chem 383 : 1553 ~ 1564
Chun Y-J / 2007 / Electron transport pathway for a Streptomyces cytochrome P450: cytochrome P450 105D5-catalyzed fatty acid hydroxylation in Streptomyces coelicolor A3(2) /
Endo A / 1976 / ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinum / J. Antibiot 29 : 1346 ~ 1348
Fasan R. / 2012 / Tuning P450 enzymes as oxidation catalysts / ACS Catal 2 : 647 ~ 666
Guengerich FP. / 2002 / Rate-limiting steps in cytochrome P450 catalysis / Biol. Chem 383 : 1553 ~ 1564
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