A cytochrome P450 CYP81AM1 from Tripterygium wilfordii catalyses the C-15 hydroxylation of dehydroabietic acid

Planta ◽  
2021 ◽  
Vol 254 (5) ◽  
Author(s):  
Jiadian Wang ◽  
Ping Su ◽  
Linhui Gao ◽  
Yifeng Zhang ◽  
Jian Wang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Dehydroabietic Acid ◽  
Tripterygium Wilfordii

scholarly journals Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lichan Tu ◽  
Ping Su ◽  
Zhongren Zhang ◽  
Linhui Gao ◽  
Jiadian Wang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Biosynthetic Pathway ◽  
Dehydroabietic Acid ◽  
Tripterygium Wilfordii ◽  
Antitumor Activities ◽  
Pancreatic Cancer Cells ◽  
Copy Numbers ◽  
Metabolomic Data ◽  
Genomic Resource ◽  
Genome Triplication

Abstract Triptolide is a trace natural product of Tripterygium wilfordii. It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction.

scholarly journals Author Correction: Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lichan Tu ◽  
Ping Su ◽  
Zhongren Zhang ◽  
Linhui Gao ◽  
Jiadian Wang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Tripterygium Wilfordii

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cytotoxic diterpenes triptolide, tripdiolide, and cytotoxic triterpenes from tissue cultures of Tripterygium wilfordii

1981 ◽  
Vol 59 (17) ◽  
pp. 2677-2683 ◽  
Author(s):  
James P. Kutney ◽  
Gary M. Hewitt ◽  
Toshio Kurihara ◽  
Phillip J. Salisbury ◽  
Robert D. Sindelar ◽  
...  
Keyword(s):  
Acid Methyl Ester ◽  
Dehydroabietic Acid ◽  
Tissue Cultures ◽  
Tripterygium Wilfordii ◽  
Quinone Methides ◽  
Tripterygium Wilfordii Hook F ◽  
Acid Methyl ◽  
Plant Tissue Cultures ◽  
Tripterygium Wilfordii Hook ◽  
Acid Compound

Plant tissue cultures of Tripterygium wilfordii Hook F produced the cytotoxic diterpene triepoxides tripdiolide (1) and triptolide (2) in yields that were 16 and 3 times greater, respectively, than those observed in the plant itself. Other diterpenes, dehydroabietic acid (3) and 15-hydroxy-18-norabieta-3,8,11,13-tetraene-3-oic acid methyl ester (4) were also isolated. Co-occuring in these cultures were the cytotoxic quinone-methides, celastrol (5), compound 6, and compound 7. Other triterpenes produced were oleanolic acid (8) and polpunonic acid (9). β-Sitosterol (17) was also isolated. The proposed structure of 4 was confirmed by synthesis starting from compound 3. Cytotoxic data are reported, and a possible biosynthetic relationship among dehydroabietic acid, compound 4, and tripdiolide (1) is presented.

scholarly journals A Cytochrome P450 Involved in the Metabolism of Abietane Diterpenoids by Pseudomonas abietaniphila BKME-9

2004 ◽  
Vol 186 (11) ◽  
pp. 3631-3639 ◽  
Author(s):  
Daryl J. Smith ◽  
Vincent J. J. Martin ◽  
William W. Mohn
Keyword(s):  
Cytochrome P450 ◽  
Dehydroabietic Acid ◽  
Gene Arrangement ◽  
Type I ◽  
Binding Assays ◽  
P450 Monooxygenase ◽  
Naturally Occurring ◽  
Abietane Diterpenoids ◽  
Pharmaceutical Properties ◽  
Conserved Gene

ABSTRACT Diterpenoids are naturally occurring plant compounds which have pharmaceutical properties. We have sequenced a 10.4-kbp extension of the dit cluster in Pseudomonas abietaniphila BKME-9, containing genes involved in abietane diterpenoid biodegradation. The ditQ gene was found to encode a cytochrome P450 monooxygenase, P450dit, and to be homologous to the tdtD gene of Pseudomonas diterpeniphila A19-6a. Knocking out ditQ had little effect on growth of BKME-9 on abietic acid but severely impaired growth on dehydroabietic acid (DhA) and palustric acid (PaA), increasing doubling times from 3.8 to 15 h on DhA and from 5.6 to 18.5 h on PaA. A xylE transcriptional fusion showed that transcription of ditQ was induced by a range of diterpenoids. Substrate binding assays of P450dit expressed in Escherichia coli revealed that DhA binds to the enzyme and yields a type I binding spectrum with a Kd of 0.4 μM. These results indicate that P450dit is involved in the metabolism of DhA and PaA and are consistent with its putative role in converting DhA to 7-hydroxy-DhA. Finally, an amino acid sequence identity of greater than 72% and conserved gene arrangement support the hypothesis that the dit gene cluster of P. abietaniphila BKME-9 and the tdt cluster of P. diterpeniphila A19-6a contain functional homologues.

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.

Comparison of mechanism-based inhibition of human cytochrome P450 2C19 by ticlopidine, clopidogrel, and prasugrel

Xenobiotica ◽  
2009 ◽  
Vol 00 (00) ◽  
pp. 090901052457079-8
Author(s):  
Y. Nishiya ◽  
K. Hagihara ◽  
A. Kurihara ◽  
N. Okudaira ◽  
N.A. Farid ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Cytochrome ◽  
Cytochrome P450 2C19

Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes

Xenobiotica ◽  
2009 ◽  
Vol 00 (00) ◽  
pp. 090901052053001-8
Author(s):  
K. Murai ◽  
H. Yamazaki ◽  
K. Nakagawa ◽  
R. Kawai ◽  
T. Kamataki
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Cytochrome P450 2A6

Selegiline Metabolism and Cytochrome P450 Enzymes:In vitro Study in Human Liver Microsomes*

2000 ◽  
Vol 86 (5) ◽  
pp. 215-221 ◽  
Author(s):  
Paivi Taavitsainen ◽  
Markku Anttila ◽  
Leena Nyman ◽  
Hari Karnani ◽  
Jarmo S. Salonen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Vitro Study
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