Document Detail


YLR099C (ICT1) encodes a soluble Acyl-CoA-dependent lysophosphatidic acid acyltransferase responsible for enhanced phospholipid synthesis on organic solvent stress in Saccharomyces cerevisiae.
MedLine Citation:
PMID:  18252723     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One of the major determinants of organic solvent tolerance is the increase in membrane phospholipids. Here we report for the first time that an increase in the synthesis of phosphatidic acid is responsible for enhanced phospholipid synthesis that confers tolerance to the organic solvent in Saccharomyces cerevisiae. This increase in phosphatidic acid formation is because of the induction of Ict1p, a soluble oleoyl-CoA:lysophosphatidic acid acyltransferase. YLR099C (ICT1) was reported to be maximally expressed during solvent tolerance (Miura, S., Zou, W., Ueda, M., and Tanaka, A. (2000) Appl. Environ. Microbiol. 66, 4883-4889); however, its physiological significance was not understood. In silico analysis revealed the absence of any transmembrane domain in Ict1p. Domain analysis showed that it has a hydrolase/acyltransferase domain with a distinct lipid-binding motif and a lysophospholipase domain. Analysis of ict1Delta strain showed a drastic reduction in phosphatidic acid suggesting the role of Ict1p in phosphatidic acid biosynthesis. Overexpression of Ict1p in S. cerevisiae showed an increase in phosphatidic acid and other phospholipids on organic solvent exposure. To understand the biochemical function of Ict1p, the gene was cloned and expressed in Escherichia coli. The purified recombinant enzyme was found to specifically acylate lysophosphatidic acid. Specific activity of Ict1p was found to be higher for oleoyl-CoA as compared with palmitoyl- and stearoyl-CoAs. This study provides a mechanism for organic solvent tolerance from the point of membrane dynamics in S. cerevisiae.
Authors:
Ananda K Ghosh; Geetha Ramakrishnan; Ram Rajasekharan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-02-04
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-08     Completed Date:  2008-05-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9768-75     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
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MeSH Terms
Descriptor/Qualifier:
Acyl Coenzyme A / genetics,  metabolism
Acyltransferases / biosynthesis*,  genetics
Enzyme Induction / drug effects
Gene Expression Regulation, Enzymologic / drug effects,  physiology*
Gene Expression Regulation, Fungal / drug effects,  physiology*
Phosphatidic Acids / biosynthesis*,  genetics
Protein Structure, Tertiary / physiology
Recombinant Proteins / genetics,  metabolism
Saccharomyces cerevisiae / enzymology*,  genetics
Solvents / pharmacology
Chemical
Reg. No./Substance:
0/Acyl Coenzyme A; 0/Phosphatidic Acids; 0/Recombinant Proteins; 0/Solvents; EC 2.3.-/Acyltransferases; EC 2.3.1.52/2-acylglycerophosphate acyltransferase
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