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PMID: 1572893 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Isolation of a Saccharomyces cerevisiae long chain fatty acyl:CoA synthetase gene (FAA1) and assessment of its role in protein N-myristoylation.

The Journal of cell biology ·Vol. 117 ·No. 3 ·1992-05-00 ·Pages 515-29

Duronio RJ, Knoll LJ, Gordon JI

Abstract

Regulation of myristoylCoA pools in Saccharomyces cerevisiae plays an important role in modulating the activity of myristoylCoA:protein N-myristoyltransferase (NMT), an essential enzyme with an ordered Bi Bi reaction that catalyzes the transfer of myristate from myristoylCoA to greater than or equal to 12 cellular proteins. At least two pathways are available for generating myristoylCoA: de novo synthesis by the multifunctional, multisubunit fatty acid synthetase complex (FAS) and activation of exogenous myristate by acylCoA synthetase. The FAA1 (fatty acid activation) gene has been isolated by genetic complementation of a faal mutant. This single copy gene, which maps to the right arm of chromosome XV, specifies a long chain acylCoA synthetase of 700 amino acids. Analyses of strains containing NMT1 and a faal null mutation indicated that FAA1 is not essential for vegetative growth when an active de novo pathway for fatty acid synthesis is present. The role of FAA1 in cellular lipid metabolism and protein N-myristoylation was therefore assessed in strains subjected to biochemical or genetic blockade of FAS. At 36 degrees C, FAA1 is required for the utilization of exogenous myristate by NMT and for the synthesis of several phospholipid species. This requirement is not apparent at 24 or 30 degrees C, suggesting that S. cerevisiae contains another acylCoA synthetase activity whose chain length and/or temperature optima may differ from Faalp.

MeSH Terms
Acyl Coenzyme A/metabolism Amino Acid Sequence Base Sequence Chromosome Mapping Chromosomes, Fungal Cloning, Molecular Coenzyme A Ligases/genetics,metabolism Fatty Acid Synthases/metabolism Genetic Complementation Test Isoenzymes/genetics Molecular Sequence Data Mutation/genetics Myristic Acid Myristic Acids/metabolism Phenotype Protein Processing, Post-Translational RNA, Messenger/biosynthesis Repressor Proteins Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins Sequence Homology, Nucleic Acid
Chemicals
Acyl Coenzyme A Isoenzymes Myristic Acids RNA, Messenger Repressor Proteins Saccharomyces cerevisiae Proteins Myristic Acid S-tetradecanoyl-coenzyme A Fatty Acid Synthases Coenzyme A Ligases FAA2 protein, S cerevisiae long-chain-fatty-acid-CoA ligase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Duronio R J
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Knoll L J
Gordon J I
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.117.3.515
Published
1992-05-00
Pages
515-29
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2289438
Subset
IM
Grants
NIAID NIH HHS · AI27179 · United States
NIAID NIH HHS · AI30188 · United States
Databases
GENBANK
M31165, M31166, M74319, M74320, M74321, M74322, M74323, M74324, M96371, X66194
External Links
PubMed source DOI: 10.1083/jcb.117.3.515 PMC Full Text View journal details
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