scholarly journals X-ray crystal structure of cytochrome P450 monooxygenase CYP101J2 fromSphingobium yanoikuyaestrain B2

2017 ◽  
Vol 85 (5) ◽  
pp. 945-950
Author(s):  
Birgit Unterweger ◽  
Nyssa Drinkwater ◽  
Priscilla Johanesen ◽  
Dena Lyras ◽  
Geoffrey J. Dumsday ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cytochrome P450 ◽  
Cytochrome P450 Monooxygenase ◽  
P450 Monooxygenase ◽  
X Ray

scholarly journals Structural elucidation of a hydroxy–cineole product obtained from cytochrome P450 monooxygenase CYP101J2 catalysed transformation of 1,8-cineole

2017 ◽  
Vol 73 (8) ◽  
pp. 1242-1245 ◽  
Author(s):  
Gavin E. Collis ◽  
Birgit Unterweger ◽  
Geoff J. Dumsday ◽  
Craig M. Forsyth
Keyword(s):  
Hydrogen Bonding ◽  
Cytochrome P450 ◽  
Solid State ◽  
Natural Product ◽  
Building Blocks ◽  
Ring System ◽  
Structural Elucidation ◽  
Cytochrome P450 Monooxygenase ◽  
P450 Monooxygenase ◽  
X Ray

1,8-Cineole is an abundant natural product that has the potential to be transformed into other building blocks that could be suitable alternatives to petroleum-based chemicals. Monohydroxylation of 1,8-cineole can potentially occur at eight different carbon sites around the bicyclic ring system. Using cytochrome P450 monooxygenase CYP101J2 from Sphingobium yanoikuyae B2, the hydroxylation can be regioselectively directed at the C atom adjacent to the methyl-substituted quaternary bridgehead atom of 1,8-cineole. The unambiguous location of the hydroxyl functionality and the stereochemistry at this position was determined by X-ray crystal analysis. The monohydroxylated compound derived from this microorganism was determined to be (1S)-2a-hydroxy-1,8-cineole (trivial name) or (1S,4R,6S)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol (V) (systematic), C10H18O2. In the solid state this compound exhibits an interesting O—H...O hydrogen-bonding motif.

scholarly journals Structural basis for selective oxidation of phosphorylated ethylphenols by cytochrome P450 monooxygenase CreJ

2021 ◽  
Author(s):  
Sheng Dong ◽  
Jingfei Chen ◽  
Xingwang Zhang ◽  
Fei Guo ◽  
Li Ma ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Cytochrome P450 ◽  
Molecular Dynamics Simulations ◽  
Selective Oxidation ◽  
Cytochrome P450 Monooxygenase ◽  
Structural Basis ◽  
Biological Degradation ◽  
P450 Monooxygenase ◽  
Dynamics Simulations

Selective oxidation of C-H bonds in alkylphenols holds great significance for not only structural derivatization in pharma- and bio-manufacturing but also biological degradation of these toxic chemicals in environmental protection. A unique chemomimetic biocatalytic system using enzymes from a p-cresol biodegradation pathway has recently been developed. As the central biocatalyst, the cytochrome P450 monooxygenase CreJ oxidizes diverse p- and m-alkylphenyl phosphates with perfect stereoselectivity at different efficiencies. However, the mechanism of regio- and stereoselectivity of this chemomimetic biocatalytic system remained unclear. Here, using p- and m-ethylphenyl substrates, we elucidate the CreJ-catalyzed key steps for selective oxidations. The crystal structure of CreJ in complex with m-ethylphenyl phosphate was solved and compared with its complex structure with p-ethylphenyl phosphate isomer. The results indicate that the conformational changes of substrate-binding residues are slight, while the substrate promiscuity is achieved mainly by the available space in the catalytic cavity. Moreover, the catalytic preferences of regio- and stereoselective hydroxylation for the two ethylphenyl substrates is explored by molecular dynamics simulations. The ethyl groups in the complexes display different flexibility, and the distances of the active oxygen to Hpro-S and Hpro-R of methylene agree with the experimental stereoselectivity. The regioselectivity can be explained by the distances and bond dissociation energy. These results provide not only the mechanistic insights of CreJ into its regio- and stereoselectivity but also the structural basis for further P450 enzyme design and engineering. Importance The key cytochrome P450 monooxygenase CreJ showed excellent regio- and stereoselectivity in the oxidation of various alkylphenol substrates. C-H bond functionalization of these toxic alkylphenols holds great significance both for biological degradation of these environmental chemicals and production of value-added structural derivatives in pharmaceutical and biochemical industries. Our results, combined with in vitro enzymatic assays, crystal structure determination of enzyme-substrate complex, and molecular dynamics simulations, provide not only significant mechanism elucidation of the regio- and stereoselective catalyzation mediated by CreJ, but also the promising directions for the future engineering efforts of this enzyme towards more useful products. It also has great extendable potentials to couple this multifunctional P450 biocatalyst with other post modifying enzymes (e.g. hydroxyl based glycosylase) to access more alkylphenol derived high-value chemicals through environment-friendly biocatalysis and biotransformation.

Molecular evolution of a cytochrome P450 for the synthesis of potential antidepressant (2R,6R)-hydroxynorketamine

2021 ◽  
Author(s):  
Ansgar Bokel ◽  
Michael C. Hutter ◽  
Vlada B. Urlacher
Keyword(s):  
Cytochrome P450 ◽  
Molecular Evolution ◽  
Cytochrome P450 Monooxygenase ◽  
P450 Monooxygenase ◽  
Effective Synthesis

Engineered cytochrome P450 monooxygenase CYP154E1 enables the effective synthesis of the potential antidepressant (2R,6R)-hydroxynorketamine via N-demethylation and regio- and stereoselective hydroxylation of (R)-ketamine.

scholarly journals Cytochrome P450 Monooxygenase-Mediated Metabolic Utilization of Benzo[a]Pyrene by Aspergillus Species

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Erin M. Ostrem Loss ◽  
Mi-Kyung Lee ◽  
Ming-Yueh Wu ◽  
Julia Martien ◽  
Wanping Chen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Environmental Pollutants ◽  
Energy Generation ◽  
Fungal Species ◽  
Metabolic Changes ◽  
Cytochrome P450 Monooxygenase ◽  
Cellular Growth ◽  
P450 Monooxygenase ◽  
Content Type ◽  
Fundamental Knowledge

ABSTRACT Soil-dwelling fungal species possess the versatile metabolic capability to degrade complex organic compounds that are toxic to humans, yet the mechanisms they employ remain largely unknown. Benzo[a]pyrene (BaP) is a pervasive carcinogenic contaminant, posing a significant concern for human health. Here, we report that several Aspergillus species are capable of degrading BaP. Exposing Aspergillus nidulans cells to BaP results in transcriptomic and metabolic changes associated with cellular growth and energy generation, implying that the fungus utilizes BaP as a growth substrate. Importantly, we identify and characterize the conserved bapA gene encoding a cytochrome P450 monooxygenase that is necessary for the metabolic utilization of BaP in Aspergillus. We further demonstrate that the fungal NF-κB-type velvet regulators VeA and VelB are required for proper expression of bapA in response to nutrient limitation and BaP degradation in A. nidulans. Our study illuminates fundamental knowledge of fungal BaP metabolism and provides novel insights into enhancing bioremediation potential. IMPORTANCE We are increasingly exposed to environmental pollutants, including the carcinogen benzo[a]pyrene (BaP), which has prompted extensive research into human metabolism of toxicants. However, little is known about metabolic mechanisms employed by fungi that are able to use some toxic pollutants as the substrates for growth, leaving innocuous by-products. This study systemically demonstrates that a common soil-dwelling fungus is able to use benzo[a]pyrene as food, which results in expression and metabolic changes associated with growth and energy generation. Importantly, this study reveals key components of the metabolic utilization of BaP, notably a cytochrome P450 monooxygenase and the fungal NF-κB-type transcriptional regulators. Our study advances fundamental knowledge of fungal BaP metabolism and provides novel insight into designing and implementing enhanced bioremediation strategies.

Continuous cyclohexane oxidation to cyclohexanol using a novel cytochrome P450 monooxygenase fromAcidovoraxsp. CHX100 in recombinantP. taiwanensisVLB120 biofilms

2015 ◽  
Vol 113 (1) ◽  
pp. 52-61 ◽  
Author(s):  
Rohan Karande ◽  
Linde Debor ◽  
Diego Salamanca ◽  
Fabian Bogdahn ◽  
Karl-Heinrich Engesser ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Monooxygenase ◽  
Cyclohexane Oxidation ◽  
P450 Monooxygenase

scholarly journals Importance of the cytochrome P450 monooxygenase CYP52 family for the sophorolipid-producing yeast Candida bombicola

2010 ◽  
Vol 10 (6) ◽  
pp. 791-791 ◽  
Author(s):  
Inge N.A. Van Bogaert ◽  
Marjan De Mey ◽  
Dirk Develter ◽  
Wim Soetaert ◽  
Erick J. Vandamme
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Monooxygenase ◽  
Candida Bombicola ◽  
P450 Monooxygenase

scholarly journals Characterization of P450 FcpC, the Enzyme Responsible for Bioconversion of Diosgenone to Isonuatigenone in Streptomyces virginiae IBL-14

2009 ◽  
Vol 75 (12) ◽  
pp. 4202-4205 ◽  
Author(s):  
Wei Wang ◽  
Feng-Qing Wang ◽  
Dong-Zhi Wei
Keyword(s):  
Escherichia Coli ◽  
Electron Transfer ◽  
Cytochrome P450 ◽  
Cytochrome P450 Monooxygenase ◽  
P450 Monooxygenase ◽  
Whole Cell ◽  
Electron Transfer Chain ◽  
Streptomyces Virginiae ◽  
Transfer Chain

ABSTRACT A new cytochrome P450 monooxygenase, FcpC, from Streptomyces virginiae IBL-14 has been identified. This enzyme is found to be responsible for the bioconversion of a pyrano-spiro steroid (diosgenone) to a rare nuatigenin-type spiro steroid (isonuatigenone), which is a novel C-25-hydroxylated diosgenone derivative. A whole-cell P450 system was developed for the production of isonuatigenone via the expression of the complete three-component electron transfer chain in an Escherichia coli strain.

scholarly journals Characterization of cytochrome P450 monooxygenase CYP154H1 from the thermophilic soil bacterium Thermobifida fusca

2010 ◽  
Vol 89 (5) ◽  
pp. 1475-1485 ◽  
Author(s):  
Anett Schallmey ◽  
Gijs den Besten ◽  
Ite G. P. Teune ◽  
Roga F. Kembaren ◽  
Dick B. Janssen
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Monooxygenase ◽  
Soil Bacterium ◽  
Thermobifida Fusca ◽  
P450 Monooxygenase
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