Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment

Acanthamoeba spp. are free-living parasites that can cause severe infections such as granulomatous amoebic encephalitis (GAE) and amoebic keratitis (AK). Polyhexamethylene biguanide (PHMB) is a topical application for AK treatment. However, PHMB is not entirely effective against all Acanthamoeba strains or isolates. The mechanisms by which Acanthamoeba protects itself against extreme drug conditions without encystation are still unknown. According to a previous study, cytochrome P450 monooxygenase (CYP450MO) plays an important role in the oxidative biotransformation of numerous drugs related to metabolism. In this study, a CYP450MO fragment was inserted into the pGAPDH-EGFP vector and transfected into Acanthamoeba castellanii. We found that CYP450MO-overexpressing Acanthamoeba had higher survival rates than those of the control cells after PHMB treatment. Moreover, we also found that encystation-related genes such as cellulose synthase I (CSI), encystation-mediating serine proteinase (EMSP), and autophagy-related protein 8 (ATG8) expression levels were not significantly different between Acanthamoeba transfected by pGAPDH-EGFP or pGAPDH-EGFP-CYP450MO. We suggest that Acanthamoeba transfected by pGAPDH-EGFP-CYP450MO may not induce encystation-related genes to resist PHMB treatment. In conclusion, these findings indicate that CYP450MO may be an additional target when PHMB is used for treatment of amoebic keratitis.

Download Full-text

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

Chemical Communications ◽

10.1039/d0cc06729f ◽

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.

Download Full-text

Genomic and transcriptomic insights into the cytochrome P450 monooxygenase gene repertoire in the rice pest brown planthopper,Nilaparvata lugens

10.1603/ice.2016.108969 ◽

2016 ◽

Author(s):

Yanyuan Bao

Keyword(s):

Cytochrome P450 ◽

Brown Planthopper ◽

Nilaparvata Lugens ◽

Cytochrome P450 Monooxygenase ◽

Gene Repertoire ◽

P450 Monooxygenase ◽

Monooxygenase Gene ◽

Rice Pest

Download Full-text

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

mBio ◽

10.1128/mbio.00558-19 ◽

2019 ◽

Vol 10 (3) ◽

Cited By ~ 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.

Download Full-text

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

Biotechnology and Bioengineering ◽

10.1002/bit.25696 ◽

2015 ◽

Vol 113 (1) ◽

pp. 52-61 ◽

Cited By ~ 27

Author(s):

Rohan Karande ◽

Linde Debor ◽

Diego Salamanca ◽

Fabian Bogdahn ◽

Karl-Heinrich Engesser ◽

...

Keyword(s):

Cytochrome P450 ◽

Cytochrome P450 Monooxygenase ◽

Cyclohexane Oxidation ◽

P450 Monooxygenase

Download Full-text

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

FEMS Yeast Research ◽

10.1111/j.1567-1364.2010.00671.x ◽

2010 ◽

Vol 10 (6) ◽

pp. 791-791 ◽

Cited By ~ 1

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

Download Full-text

Detoxification of ivermectin by ATP binding cassette transporter C4 and cytochrome P450 monooxygenase 6CJ1 in the human body louse, Pediculus humanus humanus

Insect Molecular Biology ◽

10.1111/imb.12348 ◽

2017 ◽

Vol 27 (1) ◽

pp. 73-82 ◽

Cited By ~ 8

Author(s):

J. H. Kim ◽

K. J. Gellatly ◽

B. Lueke ◽

M. Kohler ◽

R. Nauen ◽

...

Keyword(s):

Cytochrome P450 ◽

Human Body ◽

Cytochrome P450 Monooxygenase ◽

Atp Binding ◽

P450 Monooxygenase ◽

Body Louse ◽

Pediculus Humanus ◽

Atp Binding Cassette Transporter ◽

Human Body Louse ◽

Atp Binding Cassette

Download Full-text

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

Applied and Environmental Microbiology ◽

10.1128/aem.02606-08 ◽

2009 ◽

Vol 75 (12) ◽

pp. 4202-4205 ◽

Cited By ~ 11

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.

Download Full-text