Document Detail


Thioesterase-like role for fungal PKS-NRPS hybrid reductive domains.
MedLine Citation:
PMID:  18652469     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fungal reduced polyketides possess diverse structures exploring a broad region of chemical space despite their synthesis by very similar enzymes. Many fungal polyketides are capped by diverse amino acid-derived five-membered rings, the tetramic acids and related pyrrolidine-2-ones. The known tetramic acid synthetase enzymes in fungi contain C-terminal reductive (R) domains that were proposed to release reduced pyrrolidine-2-one intermediates en route to the tetramic acids. To determine the enzymatic basis of pyrrolidine-2-one diversity, we overexpressed equisetin synthetase (EqiS) R domains and analyzed their reactivity with synthetic substrate analogs. We show that the EqiS R domain does not perform a reducing function and does not bind reducing cofactors. Instead, the EqiS R catalyzes a Dieckmann condensation, with an estimated kcat approximately 15 s(-1). This role differs from the redox reactions normally catalyzed by short chain dehydrogenase/reductase superfamily enzymes.
Authors:
James W Sims; Eric W Schmidt
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-07-25
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  130     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-13     Completed Date:  2008-10-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11149-55     Citation Subset:  IM    
Affiliation:
Department of Medicinal Chemistry, University of Utah, 30 South 2000 East Rm 201, Salt Lake City, Utah 84112, USA.
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MeSH Terms
Descriptor/Qualifier:
Carbon-Carbon Lyases / chemistry
Catalytic Domain
Esterases / chemistry*
Fungi / chemistry*
Kinetics
Molecular Structure
Oxidation-Reduction
Peptide Synthases / chemistry*
Polyketide Synthases / chemistry*
Protein Folding
Protein Structure, Tertiary / physiology
Pyrrolidinones / chemical synthesis,  chemistry
Substrate Specificity
Tetrahydronaphthalenes / chemical synthesis,  chemistry
Chemical
Reg. No./Substance:
0/Pyrrolidinones; 0/Tetrahydronaphthalenes; 57749-43-6/equisetin; 79956-01-7/Polyketide Synthases; EC 3.1.-/Esterases; EC 4.1.-/Carbon-Carbon Lyases; EC 6.3.2.-/Peptide Synthases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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