Biomedical Engineering Reference
In-Depth Information
Figure 3.
Schematic representation of the
A. chrysogenum pcbAB-pcbC
promoter region
including the CPCR1 (grey) and FKH1 (black) binding sites (Adapted from Schmitt
et al. 2004b).
binding at least two sequences of the
pcbAB-pcbC
intergenic region of
A.
chrysogenum
(Fig. 3). Knock-out mutants defective in this transcription
factor showed reduced levels in the expression of the
pcbC
gene together
with a reduction in the biosynthesis of the cephalosporin C intermediate
penicillin N (Schmitt and Kück 2000, Schmitt
et al. 2004b). It is interesting
that some of these effectors modulate specifi c genes (e.g.,
pcbC
) but not
all the pathway genes since they are expressed from separate promoters
containing recognition sequences for specifi c regulators. This may create
dysfunctions between the levels of expression of the “early” and “late”
clusters.
CPCR1 homologues have been found in β-lactam non-producer
fungi, such as
Neurospora crassa
or
Fusarium graminearum
, pointing to
this transcription factor as a regulator of other functions different from
antibiotic production. In fact, CPCR1 has been shown to be involved in
the control of
A. chrysogenum
morphological development, it is required
for hyphal fragmentation and thus for the formation of arthrospores
(Hoff
et al. 2005). Therefore, the winged helix transcription factor CPCR1
seems to be the molecular link controlling cephalosporin C biosynthesis
and morphogenesis. This linking role has been also suggested in the
opportunistic human pathogen fungus
Penicillium marneffei
, where the
CPCR1 homologue (RfxA) links cellular division with morphogenesis,
particularly during conidiation and yeast growth (Bugeja et al. 2010).
Another subclass of winged-helix transcription factor that has been
characterised in
A. chrysogenum
is AcFKH1, a member of the “forkhead”
family of regulators (Gajiwala et al
.
2000) that associates with the RFX
transcription factor CPCR1 (Schmitt et al
.
2004c, Hoff and Kück 2005).
Members of the “forkhead” family are involved in human and yeast in
different processes like cell cycle regulation, death control, pre-mRNA
