Linked Life Data

11939803

Source:http://linkedlifedata.com/resource/pubmed/id/11939803

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2002-4-9
pubmed:abstractText
6-Deoxyerythronolide B synthase (DEBS) is the modular polyketide synthase (PKS) responsible for the biosynthesis of 6-dEB, the aglycon core of the antibiotic erythromycin. The biosynthesis of 6-dEB proceeds in an assembly-line fashion through the six modules of DEBS, each of which catalyzes a dedicated set of reactions, such that the structure of the final product is determined by the arrangement of modules along the assembly line. This transparent relationship between protein sequence and enzyme function is common to all modular PKSs and makes these enzymes an attractive scaffold for protein engineering through module swapping. One of the fundamental issues relating to module swapping that still needs to be addressed is the mechanism by which intermediates are channeled from one module to the next. While it has been previously shown that short linker regions at the N- and C-termini of adjacent polypeptides play an important role in mediating intermodular transfer, the contributions of other protein-protein interactions have not yet been probed. Here, we investigate the roles of the linker interactions as well as the interactions between the donor acyl carrier protein (ACP) domain and the downstream ketosynthase (KS) domain in various contexts. Linker interactions and ACP-KS interactions make relatively equal contributions at the module 2-module 3 and the module 4-module 5 interfaces in DEBS. In contrast, modules 2 and 6 are more tolerant toward substrates presented by nonnatural ACP domains. This tolerance was exploited for engineering hybrid PKS-PKS and PKS-NRPS (nonribosomal peptide synthetase) junctions and suggests fundamental ground rules for engineering novel chimeric PKSs in the future.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5056-66
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Quantitative analysis of the relative contributions of donor acyl carrier proteins, acceptor ketosynthases, and linker regions to intermodular transfer of intermediates in hybrid polyketide synthases.
pubmed:affiliation
Department of Chemistry, Stanford University, Stanford, California 94305, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't