Linked Life Data

15066039

Source:http://linkedlifedata.com/resource/pubmed/id/15066039

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-4-6
pubmed:abstractText
Aspergillus nidulans produces the polyketide toxin sterigmatocystin (ST) of which the biosynthetic and pathway specific regulatory genes compose a stc gene cluster. A previous mutagenesis screen identified 23 mutants defective in production of ST. Five mutants constitute a single locus. Genetic complementation and sequencing analysis revealed the mutant locus to be mcsA encoding methylcitrate synthase that converts propionyl-CoA to methylcitrate. Feeding downstream products of methylcitrate synthase, methylcitrate and pyruvate, did not restore ST production in mcsA mutants, indicating that loss of methylcitrate cycle products is not the cause of the ST defect. However, propionate, a precursor for propionyl-CoA, inhibited ST production and induced transcription of mcsA in the wild type. Furthermore, propionate impaired formation of two polyketide spore pigments whereas overexpression of mcsA relieved inhibition of ST production by propionate. Transcription analyses revealed that disruption of mcsA did not affect expression of the specialized fatty acid synthase genes (stcJ and stcK) or polyketide synthase gene (stcA) required for formation of norsolorinic acid (NOR), the first stable intermediate in the ST biosynthetic pathway. Feeding studies showed that NOR but not hexanoic acid (the fatty acid produced by StcJ/StcK and primer unit of StcA) or malonate (source of the extender unit of StcA) restored ST production in the mcsA mutant. We hypothesize that excess buildup of propionyl-CoA in mcsA mutants interferes with polyketide synthase activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Citrate (si)-Synthase, http://linkedlifedata.com/resource/pubmed/chemical/Citrates, http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Fungal, http://linkedlifedata.com/resource/pubmed/chemical/Hexanoic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Macrolides, http://linkedlifedata.com/resource/pubmed/chemical/Malonates, http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes, http://linkedlifedata.com/resource/pubmed/chemical/Propionates, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Sterigmatocystin, http://linkedlifedata.com/resource/pubmed/chemical/hexanoic acid, http://linkedlifedata.com/resource/pubmed/chemical/malonic acid, http://linkedlifedata.com/resource/pubmed/chemical/methylcitrate synthase
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-382X
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
541-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Blockage of methylcitrate cycle inhibits polyketide production in Aspergillus nidulans.
pubmed:affiliation
Department of Plant Pathology, University of Wisconsin, 1630 Linden Drive, Madison, WI 53706, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.