Document Detail


Structure-based dissociation of a type I polyketide synthase module.
MedLine Citation:
PMID:  17656315     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Individual modules of modular polyketide synthases (PKSs) such as 6-deoxyerythronolide B synthase (DEBS) consist of conserved, covalently linked domains separated by unconserved intervening linker sequences. To better understand the protein-protein and enzyme-substrate interactions in modular catalysis, we have exploited recent structural insights to prepare stand-alone domains of selected DEBS modules. When combined in vitro, ketosynthase (KS), acyl transferase (AT), and acyl carrier protein (ACP) domains of DEBS module 3 catalyzed methylmalonyl transfer and diketide substrate elongation. When added to a minimal PKS, ketoreductase domains from DEBS modules 1, 2, and 6 showed specificity for the beta-ketoacylthioester substrate, but not for either the ACP domain carrying the polyketide substrate or the KS domain that synthesized the substrate. With insights into catalytic efficiency and specificity of PKS modules, our results provide guidelines for constructing optimal hybrid PKS systems.
Authors:
Alice Y Chen; David E Cane; Chaitan Khosla
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemistry & biology     Volume:  14     ISSN:  1074-5521     ISO Abbreviation:  Chem. Biol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-27     Completed Date:  2007-12-13     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  9500160     Medline TA:  Chem Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  784-92     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acylation
Base Sequence
Catalysis
Chromatography, Thin Layer
DNA Primers
Polyketide Synthases / chemistry*,  isolation & purification,  metabolism
Protein Conformation
Recombinant Proteins / chemistry,  isolation & purification,  metabolism
Grant Support
ID/Acronym/Agency:
CA 66736/CA/NCI NIH HHS; GM 22172/GM/NIGMS NIH HHS; R01 CA066736/CA/NCI NIH HHS; R01 CA066736-13/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Recombinant Proteins; 79956-01-7/Polyketide Synthases
Comments/Corrections

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