一酸素添加、一酸素原子添加

English Journal

Peroxygenase reactions catalyzed by cytochromes P450.

Shoji O, Watanabe Y.Author information Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8602, Japan, shoji.osami@a.mbox.nagoya-u.ac.jp.AbstractCytochromes P450 (P450s) catalyze monooxygenation of a wide range of less reactive organic molecules under mild conditions. By contrast with the general reductive oxygen activation pathway of P450s, an H2O2-shunt pathway does not require any supply of electrons and protons for the generation of a highly reactive intermediate (compound I). Because the low cost of H2O2 allows us to use it in industrial-scale synthesis, the H2O2-shunt pathway is an attractive process for monooxygenation reactions. This review focuses on the P450-catalyzed monooxygenation of organic molecules using H2O2 as the oxidant.
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry.J Biol Inorg Chem.2014 Feb 6. [Epub ahead of print]
Cytochromes P450 (P450s) catalyze monooxygenation of a wide range of less reactive organic molecules under mild conditions. By contrast with the general reductive oxygen activation pathway of P450s, an H2O2-shunt pathway does not require any supply of electrons and protons for the generation of a hi
PMID 24500242

Identification of 20(S)-protopanaxatriol metabolites in rats by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry and nuclear magnetic resonance spectroscopy.

He C, Zhou D, Li J, Han H, Ji G, Yang L, Wang Z.Author information Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China.Abstract20(S)-Protopanaxatriol (PPT), one of the aglycones of ginsenosides, has been shown to exert cardioprotective effects against myocardial ischemic injury. However, studies on PPT metabolism have rarely been reported. This study is the first to investigate the in vivo metabolism of PPT following oral administration by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy. The structures of the metabolites were identified based on the characteristics of their MS data, MS(2) data, and chromatographic retention times. A total of 22 metabolites, including 17 phase I and 5 phase II metabolites, were found and tentatively identified by comparing their mass spectrometry profiles with those of PPT. Two new monooxygenation metabolites, (20S,24S)-epoxy-dammarane-3,6,12,25-tetraol and (20S,24R)-epoxy-dammarane-3,6,12,25-tetraol, were chemicallly synthesized and unambiguously characterized according to the NMR spectroscopic data. The metabolic pathways of PPT were proposed accordingly for the first time. Results revealed that oxidation of (1) double bonds at Δ((24,25)) to form 24,25-epoxides, followed by rearrangement to yield 20,24-oxide forms; and (2) vinyl-methyl at C-26/27 to form corresponding carboxylic acid were the predominant metabolic pathways. Phase II metabolic pathways were proven for the first time to consist of glucuronidation and cysteine conjugation. This study provides valuable and new information on the metabolism of PPT, which is indispensable for understanding the safety and efficacy of PPT, as well as its corresponding ginsenosides.
Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2014 Jan 25;88:497-508. doi: 10.1016/j.jpba.2013.09.031. Epub 2013 Oct 14.
20(S)-Protopanaxatriol (PPT), one of the aglycones of ginsenosides, has been shown to exert cardioprotective effects against myocardial ischemic injury. However, studies on PPT metabolism have rarely been reported. This study is the first to investigate the in vivo metabolism of PPT following oral a
PMID 24184656

Enhanced oxidative activities of cytochrome P450Rhf from Rhodococcus sp. expressed using the hyper-inducible expression system.

Ueno M1, Yamashita M2, Takase S3, Hino M4, Kobayashi M5, Fujie A6.Author information 1Pharmacology Research Laboratories, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. Electronic address: motoi.ueno@astellas.com.2Pharmacology Research Laboratories, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.3Analysis & Pharmacokinetics Research Laboratories, Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba-shi, Ibaraki 300-2698, Japan.4Fermentation and Biotechnology Laboratories, Astellas Pharma Inc., 156 Nakagawara, Kiyosu-shi, Aichi 452-0915, Japan.5Institute of Applied Biochemistry and Graduate School of Life and Environmental Sciences, The University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.6Research Management, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.AbstractBacterial cytochrome P450 enzymes catalyze the oxidative biotransformation of various types of compounds. Although the functional expression of Actinomycetes P450 in a closely related heterologous host can serve as a useful biocatalyst in whole-cell biotransformation assays, the co-expression of an electron transfer partner is required. To overcome this limitation, P450Rhf from Rhodococcus sp. NCIMB 9784 is an ideal candidate, because it is fused to a reductase domain at the C terminus and does not require an electron transfer partner. Here, we cloned P450Rhf into the hyper-inducible expression vector pSH19 in Streptomyces lividans TK24 for developing an efficient whole-cell biotransformation system with bacterial P450. The recombinant strain displayed high conversion activity (79.1%) of 7-ethoxycoumarin to 7-hydroxycoumarin after 48 h, and the observed activity was markedly higher than those for 7-methoxycoumarin and 7-propoxycoumarin used as substrates. We next screened several commercially available substrates possessing an ethyl phenyl ether moiety, which is also present in 7-ethoxycoumarin, and found that 4'-ethoxy-2'-hydroxyacetphenone was almost completely dealkylated (95.0%), and that 7-ethoxy-4-methylcoumarin was converted to two products, 7-hydroxy-4-methylcoumarin and 7-ethoxy-4-hydroxymethyl-coumarin. Our research suggests that enhancement of heterologous P450 expression using the pSH19 system in whole-cell biotransformation assays is valuable for identifying novel substrates of P450, as well as for obtaining high yields of conversion products.
Journal of bioscience and bioengineering.J Biosci Bioeng.2014 Jan;117(1):19-24. doi: 10.1016/j.jbiosc.2013.06.014. Epub 2013 Jul 22.
Bacterial cytochrome P450 enzymes catalyze the oxidative biotransformation of various types of compounds. Although the functional expression of Actinomycetes P450 in a closely related heterologous host can serve as a useful biocatalyst in whole-cell biotransformation assays, the co-expression of an
PMID 23886573

Japanese Journal

Enhanced oxidative activities of cytochrome P450Rhf from Rhodococcus sp. expressed using the hyper-inducible expression system(GENETICS, MOLECULAR BIOLOGY, AND GENE ENGINEERING)

Ueno Motoi,Yamashita Midori,Takase Shigehiro [他],Hino Motohiro,Kobayashi Michihiko,Fujie Akihiko
Journal of bioscience and bioengineering 117(1), 19-24, 2014-01
Bacterial cytochrome P450 enzymes catalyze the oxidative biotransformation of various types of compounds. Although the functional expression of Actinomycetes P450 in a closely related heterologous hos …
NAID 110009766598

ビタミンDとシトクロムP450の遺伝子多型(<特集>「ビタミンと遺伝子多型」-ビタミンD-)

榊利之,西川美宇
ビタミン 87(9), 519-524, 2013-09-25
… CYP2R1 catalyzes conversion of vitamin D_3 to 25-hydroxyvitamin D_3 (25OHD3), while CYP27B1 catalyzes conversion of 25OHD_3 to 1α, 25-dihydroxyvitamin D_3 (1,25(OH)2D3), the active form of vitamin D_3 On the contrary, CYP24A1 inactivates 1,25(OH)2D3 by multi-step monooxygenation reactions. …
NAID 110009636194

Characterization of an Isoeugenol Monooxygenase (Iem) from Pseudomonas nitroreducens Jin1 That Transforms Isoeugenol to Vanillin

RYU Ji-Young,SEO Jiyoung,PARK Sunhwa,AHN Joong-Hoon,CHONG Youhoon,SADOWSKY Michael J.,HUR Hor-Gil
Bioscience, Biotechnology, and Biochemistry 77(2), 289-294, 2013
… An 18Oxygen-labeling experiment revealed that oxidative cleavage of isoeugenol by Iem was catalyzed via a monooxygenation reaction, and that incorporation of the oxygen atom from O2 into vanillin was preferable to incorporation from water. …
NAID 130004138029