Volume 270,
Number 22,
Issue of June 2, pp. 13171-13178, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Regulation of
Lipid Biosynthesis in Saccharomyces cerevisiae by Fumonisin
B
Wen-I
Wu
,
Virginia
M.
McDonough
,
Joseph T.
NickelsJr.
,
Jesang
Ko
,
Anthony
S.
Fischl
,
Teresa R.
Vales
,
Alfred H.
MerrillJr.
,
George M.
Carman
The regulation of lipid biosynthesis in the yeast
Saccharomyces cerevisiae by fumonisin B
was
examined. Fumonisin B inhibited the growth of yeast cells.
Cells supplemented with fumonisin B accumulated free
sphinganine and phytosphingosine in a dose-dependent manner. The
cellular concentration of ceramide was reduced in fumonisin
B-supplemented cells. Ceramide synthase activity was found
in yeast cell membranes and was inhibited by fumonisin B.
Fumonisin B inhibited the synthesis of the
inositol-containing sphingo-lipids inositol phosphorylceramide,
mannosylinositol phosphorylceramide, and mannosyldiinositol
phosphorylceramide. Fumonisin B also caused a decrease in
the synthesis of the major phospholipids synthesized via the
CDP-diacylglycerol-dependent pathway and the synthesis of neutral
lipids. The effects of fumonisin B and sphingoid bases on
the activities of enzymes in the pathways leading to the synthesis of
sphingolipids, phospholipids, and neutral lipids were also examined.
Other than ceramide synthase, fumonisin B did not affect
the activities of any of the enzymes examined. However, sphinganine and
phytosphingosine inhibited the activities of inositol
phosphorylceramide synthase, phosphatidylserine synthase, and
phosphatidate phosphatase. These are key enzymes responsible for the
synthesis of lipids in yeast. The data reported here indicated that the
biosynthesis of sphingolipids, phospholipids and neutral lipids was
coordinately regulated by fumonisin B through the
regulation of lipid biosynthetic enzymes by sphingoid bases.
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