Prostaglandin E2 (PGE2) is a bioactive lipid signaling molecule implicated in a range of inflammatory diseases and cancers. In humans, PGE2 is biosynthesized by sequential oxidation of arachidonic acid (AA) by cyclooxygenases (COX) and prostaglandin E2 synthase (PTGES). Studies have shown at least two pathogenic fungi of humans to produce PGE 2, which is thought to potentiate their invasive properties. Our studies show that Saccharomyces cerevisiae, a saprophytic fungus, also produces at least 500 pg/ml of PGE2 when cultured in the presence of AA. PGE2 produced by S. cerevisiae is of concern because this fungus is utilized to manufacture a wide range of products including alcoholic beverages, and recombinant proteins for vaccines and therapeutics. The sequenced genomes of fungi, including S. cerevisiae lack genes homologous to mammalian COX and PTGES, which suggests a novel biochemical pathway for PGE2 biosynthesis by fungi. Treatment with 1 mM cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors reduced production of PGE2, suggesting that enzymes with active sites that are similar to both COX and LOX may be responsible for PGE2 production by S. cerevisiae. Detection of PGE2 in beer (150-500 pg/ml) and sake suggests that S. cerevisiae is capable of utilizing a wide range of fatty acids to produce PGE2. The discovery that S. cerevisiae a saprophytic and model biological fungus produces PGE2 has potentially broad implications for understanding the mechanisms of eicosanoid production in both pathogenic and non-pathogenic fungi, and has relevance to disease.
|Commitee:||Gharakhanian, Editte, Narayanaswami, Vasanthy|
|School:||California State University, Long Beach|
|School Location:||United States -- California|
|Source:||MAI 51/05M(E), Masters Abstracts International|
|Subjects:||Molecular biology, Microbiology, Biochemistry|
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