Journal of Microbiology and Biotechnology
The Korean Society for Microbiology and Biotechnology publishes the Journal of Microbiology and Biotechnology.

2017 ; Vol.27-5: 956~964

AuthorQiuping Yao, Li Ma, Ling Liu, Haruo Ikeda, Shinya Fushinobu, Shengying Li, Lian-Hua Xu
Place of dutyOcean College, Zhejiang University, Dinghai, Zhoushan, Zhejiang 316021, P.R. China
TitleHydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469)
PublicationInfo J. Microbiol. Biotechnol.2017 ; Vol.27-5
AbstractCompactin 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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Supplemental Data
Key_wordCompactin, CYP105D7, pravastatin, Streptomyces avermitilis, hydroxylation
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