The NAD-dependent malic enzyme from Schizosaccharomyces pombe catalyzes the
oxidative decarboxylation of L-malate to pyruvate and CO2. Transcription o
f the S, pombe malic enzyme gene, mae2, was studied to elucidate the regula
tory mechanisms involved in the expression of the gene. No evidence for sub
strate-induced expression of mae2 was observed in the presence of 0.2% L-ma
late, However, transcription of mae2 was induced when cells were grown in h
igh concentrations of glucose or under anaerobic conditions. The increased
levels of malic enzyme may provide additional pyruvate or assist in maintai
ning the redox potential under fermentative conditions. Deletion and mutati
on analyses of the 5'-flanking region of the mae2 gene revealed the presenc
e of three novel negative cis-acting elements, URS1, URS2, and URS3, that s
eem to function cooperatively to repress transcription of the mae2 gene. UR
S1 and URS2 are also present in the promoter region of the S, pombe malate
transporter gene, suggesting co-regulation of their expression. Furthermore
, two positive cis-acting elements in the mae2 promoter, UAS1 and UAS2, sho
w homology with the DNA recognition sites of the cAMP-dependent transcripti
on factors ADR1, AP-2, and ATF (activating transcription factor)/CREB (cAMP
response element binding).