Sect. II.B.2) that coordinates development and
secondary metabolism (Purschwitz et al. 2008;
Bayram et al. 2008b; Fig. 8.2). LreA binds to its
target sequences in the dark in dependency of
FphA while being released after illumination
with blue or red light (Blumenstein et al. 2005;
Hedtke et al. 2015). LreA modulates gene
expression together with FphA through modification of histone H3 by interacting with the
acetyltransferase GcnE (general control nonderepressible E) and the histone deacetylase
HdaA (Grimaldi et al. 2006; Hedtke et al.
2015). FphA of A. nidulans is a phytochrome
with light-driven histidine kinase activity and
presumably transmits the white collar and phytochrome light signal directly to the velvet protein VeA by phosphorylation (Rauscher et al.
2016). This results in an enhancement of asexual development in light and a delay in dark,
where sexual development is favored. After
30 min of illumination as minimum time
required to initiate conidiation, 19% of the
transcriptome of competent A. nidulans mycelia reacts to light (Bayram et al. 2010, 2016;
Hedtke et al. 2015; Macheleidt et al. 2016). Austinol and dehydroaustinol (see Sect. I.B.1) are
secondary metabolites connected to conidiospore production that are only produced in light
but not in dark (Rodrı ´guez-Urra et al. 2012).
Cryptochromes are blue and UV light
receptors with similarities to blue lightdependent DNA repairing photolyases, carrying a photolyase domain (Idnurm et al. 2010;
Fischer et al. 2016). They bind non-covalently
to flavin adenine dinucleotide (FAD) as well as
other chromophores such as pterin or deazaflavin. The cryptochromes CryA of A. nidulans
and Cry1 of T. reesei are so far the only known
dual-function cryptochrome/photolyase proteins. A. nidulans CryA inhibits sexual development in UV light and has a DNA repair function
(Bayram et al. 2008a), whereas T. reesei Cry1 is
needed for light-induced transcription besides
its DNA repair function in conidia (Garcı ´aEsquivel et al. 2016). In N. crassa, Cry1 acts as
transcriptional repressor of the white collar
blue light complex without photolyase activity
(Nsa et al. 2015).
Opsins, the green light receptors, are
membrane-bound proteins associated with a
retinal chromophore. They are related to bacterial and archaeal rhodopsins that, in their activated form, channel ions across the membrane
(Yu and Fischer 2019). In filamentous fungi,
opsins are poorly characterized. In F. fujikuroi,
the opsin CarO (carotenoid O) was described as
green light-driven proton pump that is
involved in spore germination (Garcı ´a-Martı ´nez et al. 2015). In contrast, the N. crassa
NOP-1 (Neurospora opsin-1) lacks proton
pump activity but is involved in the regulation
of the switch between asexual and sexual development in response to light and ROS levels
(Wang et al. 2018).
B. Gene Expression for Secondary Metabolite
Production Is Interconnected with
Morphological Differentiation
Environmental stimuli such as light, oxygen,
pH, and nutrients affect fungal morphological
programs as well as the tightly interconnected
specific secondary metabolite production.
Accordingly, defects in light control affect secondary metabolism. One example is Fusarium
fujikuroi, which is impaired in secondary
metabolite production when the white collar
blue light sensor WC-1 is defective, and which
uses its cryptochrome CryD to repress the production of the antibiotic bikaverin during
growth in light (Estrada and Avalos 2008; Castrillo et al. 2013).
1. Expression of Silenced Secondary Metabolite
Clusters by Specific and Global Regulators
Filamentous fungi are a vast reservoir of yet
undescribed secondary metabolites, carrying
dozens of usually clustered but only specifically
expressed biosynthetic gene clusters. Many of
these clusters are controlled by cluster-specific,
poorly conserved transcription factors (Alberti
et al. 2017; Keller 2018). In addition, there are
several master regulators of secondary metabolism such as the originally in A. nidulans
described methyltransferase LaeA or the
multi-cluster regulator A (McrA). LaeA is
encoded by a conserved regulatory gene with
homologues in filamentous fungi such as Fusar182
J. Gerke et al.
secondary metabolism (Purschwitz et al. 2008;
Bayram et al. 2008b; Fig. 8.2). LreA binds to its
target sequences in the dark in dependency of
FphA while being released after illumination
with blue or red light (Blumenstein et al. 2005;
Hedtke et al. 2015). LreA modulates gene
expression together with FphA through modification of histone H3 by interacting with the
acetyltransferase GcnE (general control nonderepressible E) and the histone deacetylase
HdaA (Grimaldi et al. 2006; Hedtke et al.
2015). FphA of A. nidulans is a phytochrome
with light-driven histidine kinase activity and
presumably transmits the white collar and phytochrome light signal directly to the velvet protein VeA by phosphorylation (Rauscher et al.
2016). This results in an enhancement of asexual development in light and a delay in dark,
where sexual development is favored. After
30 min of illumination as minimum time
required to initiate conidiation, 19% of the
transcriptome of competent A. nidulans mycelia reacts to light (Bayram et al. 2010, 2016;
Hedtke et al. 2015; Macheleidt et al. 2016). Austinol and dehydroaustinol (see Sect. I.B.1) are
secondary metabolites connected to conidiospore production that are only produced in light
but not in dark (Rodrı ´guez-Urra et al. 2012).
Cryptochromes are blue and UV light
receptors with similarities to blue lightdependent DNA repairing photolyases, carrying a photolyase domain (Idnurm et al. 2010;
Fischer et al. 2016). They bind non-covalently
to flavin adenine dinucleotide (FAD) as well as
other chromophores such as pterin or deazaflavin. The cryptochromes CryA of A. nidulans
and Cry1 of T. reesei are so far the only known
dual-function cryptochrome/photolyase proteins. A. nidulans CryA inhibits sexual development in UV light and has a DNA repair function
(Bayram et al. 2008a), whereas T. reesei Cry1 is
needed for light-induced transcription besides
its DNA repair function in conidia (Garcı ´aEsquivel et al. 2016). In N. crassa, Cry1 acts as
transcriptional repressor of the white collar
blue light complex without photolyase activity
(Nsa et al. 2015).
Opsins, the green light receptors, are
membrane-bound proteins associated with a
retinal chromophore. They are related to bacterial and archaeal rhodopsins that, in their activated form, channel ions across the membrane
(Yu and Fischer 2019). In filamentous fungi,
opsins are poorly characterized. In F. fujikuroi,
the opsin CarO (carotenoid O) was described as
green light-driven proton pump that is
involved in spore germination (Garcı ´a-Martı ´nez et al. 2015). In contrast, the N. crassa
NOP-1 (Neurospora opsin-1) lacks proton
pump activity but is involved in the regulation
of the switch between asexual and sexual development in response to light and ROS levels
(Wang et al. 2018).
B. Gene Expression for Secondary Metabolite
Production Is Interconnected with
Morphological Differentiation
Environmental stimuli such as light, oxygen,
pH, and nutrients affect fungal morphological
programs as well as the tightly interconnected
specific secondary metabolite production.
Accordingly, defects in light control affect secondary metabolism. One example is Fusarium
fujikuroi, which is impaired in secondary
metabolite production when the white collar
blue light sensor WC-1 is defective, and which
uses its cryptochrome CryD to repress the production of the antibiotic bikaverin during
growth in light (Estrada and Avalos 2008; Castrillo et al. 2013).
1. Expression of Silenced Secondary Metabolite
Clusters by Specific and Global Regulators
Filamentous fungi are a vast reservoir of yet
undescribed secondary metabolites, carrying
dozens of usually clustered but only specifically
expressed biosynthetic gene clusters. Many of
these clusters are controlled by cluster-specific,
poorly conserved transcription factors (Alberti
et al. 2017; Keller 2018). In addition, there are
several master regulators of secondary metabolism such as the originally in A. nidulans
described methyltransferase LaeA or the
multi-cluster regulator A (McrA). LaeA is
encoded by a conserved regulatory gene with
homologues in filamentous fungi such as Fusar182
J. Gerke et al.