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Characterizing the Lone Acyltransferase Homolog in Saccharomyces cerevisiae
Author(s) -
Ullrich Alexander,
Hardin Blake,
Khanafer Adam,
Oelkers Peter
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.796.14
Subject(s) - acyltransferases , acyltransferase , saccharomyces cerevisiae , glycerophospholipids , biochemistry , acyl coa , chemistry , biology , yeast , enzyme , biosynthesis , phospholipid , membrane
Cell membranes are largely composed of glycerophospholipids (PL) that create a barrier and separate intracellular aqueous environments. PL are heterogeneous, amphipathic lipids containing a glycerol backbone. In Saccharomyces cerevisiae , our previous work found that 108 different PL structural species were maintained at consistent relative abundance. Our aim is to understand the molecular mechanisms that maintain and regulate PL species abundance. The distribution of acyl chains in PL may be controlled by the activity and substrate specificity of acyltransferases which use an acyl‐CoA substrate to attach a hydrocarbon chain to an acceptor's hydroxyl group via an ester bond. In S. cerevisiae , at least 11 characterized acyltransferases contribute to PL metabolism. One, PSI1p, which esterifies 1‐hydroxy‐2‐acyl phosphatidylinositol with stearoyl‐CoA, has an uncharacterized paralog, YDR018c. Determining the acyl acceptor for YDR018c will likely clarify mechanisms for PL homeostasis in S. cerevisiae and provide a functional precedent for its most similar human homologs, 1‐acyl‐3‐glycerophosphate acyltransferase (AGPAT) 3 and 4. Since Psi1p has been shown to utilize an acyl acceptor with a large head group, inositol, it is possible that YDR018c utilizes a similar acyl acceptor. Since work by others and our lab did not identify a PL phenotype for haploid S. cerevisiae harboring a targeted deletion of YDR018c, loss of its function may be masked by the activity of other acyltransferases. To address this, we have made compound, targeted gene deletions of YDR018c, PSI1 and combinations of glycerol‐3‐phosphate O‐acyltransferases (GPATs; GAT1 or GAT2) and AGPATs (SLC1 or LPT1). Growth phenotype assays, including temperature sensitivity and providing various metabolic stresses, are ongoing to identify physiological changes in the compound deletion strains. Phospholipidome analysis, after culturing the strains in conditions shown to elicit a growth phenotype, will follow so to identify the absence or loss of specific PL species in conjunction with YDR018c deletion. Support or Funding Information This project was supported by the 2018 Summer Undergraduate Research Experience (SURE) Program from the University of Michigan‐Dearborn's Office of Research and Sponsored Programs (ORSP). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .