Biomedical Engineering Reference
In-Depth Information
microorganism, the heterotrimeric G
α
protein Pga1 negatively regulates
conidiation mainly by a cAMP-independent mechanism (García-Rico et
al. 2008b). The same mechanism may operate in
A. chrysogenum
, although
it has not been investigated. However, this signalling pathway might
not be the only mechanism that co-ordinates secondary metabolism and
sporulation, thus highlighting the complex nature of mutual connections
between different cellular processes in fungi (Calvo et al. 2002).
It is well known that there are several parameters infl uencing the
production of β-lactam antibiotics, such as carbon and nitrogen sources
or ambient pH (Martín et al. 2010). To date, few regulators controlling the
expression of the cephalosporin biosynthesis genes in
A. chrysogenum
have
been characterized (Schmitt et al. 2004a). The repressor CRE1 regulates
the
pcbC
and
cefEF
genes, whose expression is repressed in the presence of
glucose in the wild-type strain. However, only the
cefEF
gene is repressed
by CRE1 in a moderate high-producer strain grown with sufficient
glucose (Jekosch and Kück 2000a, b), suggesting that this high-producing
strain is deregulated on the carbon catabolite regulation of
pcbC
. The
response to the external pH is mediated by the transcription factor
PacC, which binds the bi-directional promoters of the genes
pcbAB-pcbC
and
cefEF-cefG
, both promoters containing two PacC binding sites each
(Schmitt et al. 2001).
In addition to these two regulators, the winged helix transcriptional
factor CPCR1, its associated factor FKH1 (Schmitt et al. 2004b, c) and
a homologue of the
Aspergillus
velvet protein VeA (Dreyer et al. 2007)
are specially interesting due to their ability to control also arthrospore
formation.
Transcription Factor CPCR1 and the Interaction with AcFKH1
The
A. chrysogenum
transcription factor CPCR1 is related to human
transcription factors of the RFX family, which constitutes a small class of
winged helix factors characterized by a nonconventional mode of DNA
recognition. Crystallographic studies revealed that in the human RFX
protein, most contacts to the major groove of the DNA are made by wing 1,
whereas recognition helix 3 is in charge of contacting to the major groove
in all other well-characterized winged helix proteins (Gajiwala
et al. 2000).
The C-terminus of this protein is necessary for homodimerization, since
truncation of the dimerization domain results in the inability of CPCR1 to
form homodimers and in a loss of the DNA-binding activity. Therefore, it
has been concluded that CPCR1 only binds DNA in a dimeric state (Schmitt
and Kück 2000). CPCR1 regulates the cephalosporin C biosynthesis by
