Flavin-containing monooxygenase from yeast (yFMO) carries out the O-2- and
NADPH-dependent oxidation of biological thiols, including oxidizing glutath
ione to glutathione disulfide, FMO provides a large fraction of the oxidizi
ng necessary for proper folding of disulfide bond-containing proteins; dele
tion of the enzyme reduces proper folding of endogenous carboxypeptidase Y
by about 40%, The enzyme is not essential to cell viability because other e
nzymes can generate a significant fraction of the oxidizing equivalents req
uired by the cell. However, yFMO is vital to the yeast response to reductiv
e stress. FMO1 deletion mutants grow poorly under reductive stress, and car
boxypeptidase Y activity is less than 10% of that in a stressed wild type.
The FMO1 gene appears to be under control of an unfolded protein response e
lement and is inducible by factors, such as reductive stress, that elicit t
he unfolded protein response. Reductive stress can increase yFMO activity a
t least 6-fold. This increased activity allows the cell to process endogeno
us disulfide bond-containing proteins and also to allow correct folding of
disulfide-bonded proteins expressed from multicopy plasmids, The unfolded p
rotein response is mediated by the Hac1p transcription factor that mediates
virtually all of the induction of yFMO triggered by exogenous reducing age
nts.