Research article summary (published 4 Jun 2009):

Taxol biosynthesis: Identification and characterization of two acetyl CoA:taxoid-O-acetyl transferases that divert pathway flux away from Taxol production.

Full Abstract

Two cDNAs encoding taxoid-O-acetyl transferases (TAX 9 and TAX 14) were obtained from a previously isolated family of Taxus acyl/aroyl transferase cDNA clones. The recombinant enzymes catalyze the acetylation of taxadien-5alpha,13alpha-diacetoxy-9alpha,10beta-diol to generate taxadien-5alpha,10beta,13alpha-tri-acetoxy-9alpha-ol and taxadien-5alpha,9alpha,13alpha-triacetoxy-10beta-ol, respectively, both of which then serve as substrates for a final acetylation step to yield taxusin, a prominent side-route metabolite of Taxus. Neither enzyme acetylate the 5alpha- or the 13alpha-hydroxyls of taxoid polyols, indicating that prior acylations is required for efficient peracetylation to taxusin. Both enzymes were kinetically characterized, and the regioselectivity of acetylation was shown to vary with pH. Sequence comparison with other taxoid acyl transferases confirmed that primary structure of this enzyme type reveals little about function in taxoid metabolism. Unlike previously identified acetyl transferases involved in Taxol production, these two enzymes appear to act exclusively on partially acetylated taxoid polyols to divert the Taxol pathway to side-route metabolites.

Author information

Author/s: Hampel, Daniela (D); Mau, Christopher J D (CJ); Croteau, Rodney B (RB);

Affiliation: Institute of Biological Chemistry, Washington State University, Pullman, WA 99164-6340, USA. dhampel(-atsign-)ucdavis.edu

Grants: CA-55254 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys), published in United States. (Language: eng)

Reference: 2009-Jul; vol 487 (issue 2) : pp 91-7

Dates: Created 2009/07/14; Completed 2009/08/12; Revised 2009/09/23;

PMID: 19501040, status: MEDLINE (last retrieval date: 9/24/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acetyl-CoA C-Acetyltransferase - analysis; chemistry; genetics; metabolism Amino Acid Sequence Cloning, Molecular

Molecular Sequence Data Paclitaxel - biosynthesis Taxus - enzymology

Associated Chemicals: Paclitaxel (33069-62-4) ; Acetyl-CoA C-Acetyltransferase (EC 2.3.1.9)

Related articles

These are the highest related articles currently in the database:

• Cloning and sequencing of hydroxylase genes involved in taxol biosynthesis. 29 Jun 2004
• Molecular cloning and characterization of a cytochrome P450 taxoid 2alpha-hydroxylase involved in Taxol biosynthesis. 29 Jun 2004
• Specificity of the N-benzoyl transferase responsible for the last step of Taxol biosynthesis. 26 Jun 2008
• Proteomic analysis reveals the spatial heterogeneity of immobilized Taxus cuspidata cells in support matrices. 30 Mar 2006
• Coexpression in yeast of Taxus cytochrome P450 reductase with cytochrome P450 oxygenases involved in Taxol biosynthesis. 3 Mar 2005
• Genetic engineering of taxol biosynthetic genes in Saccharomyces cerevisiae. 3 Feb 2006
• Intramolecular proton transfer in the cyclization of geranylgeranyl diphosphate to the taxadiene precursor of taxol catalyzed by recombinant taxadiene synthase. 29 Nov 2000
• Preliminary assessment of the C13-side chain 2'-hydroxylase involved in taxol biosynthesis. 22 Aug 2005
• Purification, cloning, and functional expression of phenylalanine aminomutase: the first committed step in Taxol side-chain biosynthesis. 30 May 2005
• The final acylation step in taxol biosynthesis: cloning of the taxoid C13-side-chain N-benzoyltransferase from Taxus. 25 Jun 2002

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.