| Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase. | |
| | |
MedLine Citation:
|
PMID: 17071746 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Polyketides are a class of natural products that exhibit a wide range of functional and structural diversity. They include antibiotics, immunosuppressants, antifungals, antihypercholesterolemics, and cytotoxins. Polyketide synthases (PKSs) use chemistry similar to fatty acid synthases (FASs), although building block variation and differing extents of reduction of the growing polyketide chain underlie their biosynthetic versatility. In contrast to the well studied sequential modular type I PKSs, less is known about how the iterative type I PKSs carry out and control chain initiation, elongation, folding, and cyclization during polyketide processing. Domain structure analysis of a group of related fungal, nonreducing PKSs has revealed well defined N-terminal domains longer than commonly seen for FASs and modular PKSs. Predicted structure of this domain disclosed a region similar to malonyl-CoA:acyl-carrier protein (ACP) transacylases (MATs). MATs play a key role transferring precursor CoA thioesters from solution onto FASs and PKSs for chain elongation. On the basis of site-directed mutagenesis, radiolabeling, and kinetics experiments carried out with individual domains of the norsolorinic acid PKS, we propose that the N-terminal domain is a starter unit:ACP transacylase (SAT domain) that selects a C(6) fatty acid from a dedicated yeast-like FAS and transfers this unit onto the PKS ACP, leading to the production of the aflatoxin precursor, norsolorinic acid. These findings could indicate a much broader role for SAT domains in starter unit selection among nonreducing iterative, fungal PKSs, and they provide a biochemical rationale for the classical acetyl "starter unit effect." |
| | |
Authors:
|
Jason M Crawford; Blair C R Dancy; Eric A Hill; Daniel W Udwary; Craig A Townsend |
Related Documents
:
|
11248246 - Mutations in the fatty acid elongation 1 gene are associated with a loss of beta-ketoac... 7748356 - Fatty acid oxidation abnormalities in childhood-onset spinal muscular atrophy: primary ... 9232626 - Relation between free fatty acid and acyl-coa concentrations in rat brain following dec... 6853486 - Metabolic fate of platelet-activating factor in neutrophils. 10588216 - Folic acid improves arterial endothelial function in adults with hyperhomocystinemia. 12419386 - Synthesis of [difluoro-(3-alkenylphenyl)-methyl]-phosphonic acids on non-crosslinked po... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-10-27 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 103 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2006 Nov |
Date Detail:
|
Created Date: 2006-11-08 Completed Date: 2006-12-20 Revised Date: 2011-09-19 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 16728-33 Citation Subset: IM |
Affiliation:
|
Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acyl-Carrier Protein S-Acetyltransferase
/
chemistry*,
genetics,
metabolism Aflatoxins / biosynthesis, chemistry Amino Acid Sequence Aspergillus / enzymology, genetics Base Sequence Cloning, Molecular DNA, Fungal / genetics Genes, Fungal Molecular Sequence Data Molecular Structure Mutagenesis, Site-Directed Polyketide Synthases / chemistry*, genetics, metabolism Protein Structure, Tertiary Recombinant Proteins / chemistry, genetics, metabolism Sequence Homology, Amino Acid |
| Grant Support | |
ID/Acronym/Agency:
|
ES 001670/ES/NIEHS NIH HHS; R37 AI014937-30/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Aflatoxins; 0/DNA, Fungal; 0/Recombinant Proteins; 79956-01-7/Polyketide Synthases; EC 2.3.1.38/Acyl-Carrier Protein S-Acetyltransferase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gla...
Next Document: CLA-1 and its splicing variant CLA-2 mediate bacterial adhesion and cytosolic bacterial invasion in ...