Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5139
pubmed:dateCreated
1993-12-29
pubmed:abstractText
Microorganisms and plants manufacture a large collection of medically and commercially useful natural products called polyketides by a process that resembles fatty acid biosynthesis. Genetically engineered microorganisms with modified polyketide synthase (PKS) genes can produce new metabolites that may have new or improved pharmacological activity. A potentially general method to prepare cell-free systems for studying bacterial type II PKS enzymes has been developed that facilitates the purification and reconstitution of their constituent proteins. Selective expression of different combinations of the Streptomyces glaucescens tetracenomycin (Tcm) tcmJKLMN genes in a tcmGHIJKLMNO null background has been used to show that the Tcm PKS consists of at least the TcmKLMN proteins. Addition of the TcmJ protein to the latter four enzymes resulted in a greater than fourfold increase of overall activity and thus represents the optimal Tcm PKS. Polyclonal antibodies raised against each of the TcmKLMN proteins strongly inhibit the Tcm PKS, as do known inhibitors targeted to the active site Cys and Ser residues of a fatty acid synthase. This system exhibits a strict starter unit specificity because neither propionyl, butyryl, or isobutyryl coenzyme A substitute for acetyl coenzyme A in assembly of the Tcm decaketide. Because the Tcm PKS activity is significantly diminished by removal of the TcmM acyl carrier protein and can be restored by addition of separately purified TcmM to two different types of TcmM-deficient PKS, it should be possible to use such preparations to assay for each of the constituents of the Tcm PKS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0036-8075
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
262
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1535-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Enzymatic synthesis of a bacterial polyketide from acetyl and malonyl coenzyme A.
pubmed:affiliation
School of Pharmacy, University of Wisconsin, Madison 53706.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.