DNA-binding, or velvet domains are fungal
specific. Notably, the mating-type protein is
exclusively present in ascomycetes (Ahmed
et al. 2013; Shelest 2017). The velvet domain is
structurally similar to the immunoglobulin-like
Rel homology domain of the mammalian transcription factor NF-kB p50 (Ahmed et al. 2013).
The four velvet domain proteins of Aspergilli
steer large hierarchical networks and interconnect developmental programs with secondary
metabolism triggered by chemical, oxidative,
light, or temperature sensing and subsequent
signal transduction pathways (Bayram et al.
2008b; Bayram and Braus 2012; Lind et al.
2016).
1. Chemical Sensing and Oxidative Stress as
Developmental Signal: How Fungi Smell
Their Environment
Chemical sensing is accomplished by G
protein-coupled receptors (GPCRs) with a common seven transmembrane domain architecture that initiate signal transduction through
binding to the heterotrimeric Ga, Gb, and Gg
protein complex. In Aspergilli, three different
Ga, one Gb, and one Gg protein exist (de Vries
et al. 2017; Brown et al. 2018). GPRCs are the
largest fungal group of surface receptors
important for sensing of pheromones, nutrients, and host cells in pathogenic interactions.
For instance, the binding of a pheromone to the
receptor initiates GDP-GTP exchange on the Ga
protein that then dissociates from the bg dimer
and typically activates a three-step mitogenactivated protein (MAP) kinase cascade, which
finally changes transcription. The result of this
well conserved cascade in fungi is a cell cycle
arrest and the cellular fusion of both mating
partners (Bahn et al. 2007). Further, similar
sensing systems through G protein-coupled
receptors with different transcriptional outcomes exist for different macro- and micronutrients including glucose as main carbon energy
source. Glucose is sensed through the sugar
receptor Gpr1 (G protein-coupled receptor 1)
that stimulates Gpa2 resulting in increased
cyclic adenosine monophosphate (cAMP) levels
through activation of adenylyl cyclase and protein kinase A (PKA). Active PKA inhibits the
Atg1 (autophagy-specific gene 1) initiation
kinase of autophagy degradation pathways
(see Sect. V.B). Specialized sugar transporters
such as yeast Snf3 (sucrose nonfermenting 3)
and Rgt2 (restores glucose transport 2) act as
sensors inducing signal transduction and
changed transcription (Bahn et al. 2007).
The regulation of the mycotoxin sterigmatocystin in A. nidulans works through a GaPKA pathway. The Ga protein FadA (fluffy
autolytic dominant A) activates PkaA (protein
kinase A A), which in turn is a repressor of the
specific transcription factor of the sterigmatocystin biosynthesis cluster, AflR (aflatoxin regulator). The activation of the Ga protein FadA
is inhibited by the fluffy low brlA protein FlbA
(Shimizu et al. 2003; Fig. 8.2).
Reactive oxygen species (ROS) function as
signalling molecules in light perception and
redox biology and thereby induce fungal development (Gessler et al. 2007). Therefore, an
impact on ROS homeostasis is often linked to
distorted development in filamentous fungi
(Nahlik et al. 2010; Kolog Gulko et al. 2018).
Fungi respond to oxidative stress induced by
ROS through activation of a MAP kinase pathway (Yu and Fischer 2019). The MAP kinase
Hog1 (high osmolarity glycerol response 1) of S.
cerevisiae or its homologue SakA (stress activated kinase A) in A. nidulans are activated by
ROS and in turn induce transcription factors
needed for the induction of the oxidative stress
response, such as the A. nidulans AtfA (activating transcription factor A). These transcription
factors regulate different antioxidants, such as
superoxide dismutases, catalases, peroxidases,
glutathione peroxidases, peroxiredoxins, and
antioxidative secondary metabolites. The
stress-activated kinase SakA is not only
induced by ROS but also by light, mediated
through the red light photoreceptor FphA (fungal phytochrome A), which represses fruiting
body formation in A. nidulans (Yu and Fischer
2019). SakA additionally mediates repression of
the A. nidulans NADPH oxidase gene noxA,
which is essential for different steps during
sexual fruiting body formation (Lara-Ortı ´z
et al. 2003).
8 Coordination of Fungal Secondary Metabolism and Development
179
specific. Notably, the mating-type protein is
exclusively present in ascomycetes (Ahmed
et al. 2013; Shelest 2017). The velvet domain is
structurally similar to the immunoglobulin-like
Rel homology domain of the mammalian transcription factor NF-kB p50 (Ahmed et al. 2013).
The four velvet domain proteins of Aspergilli
steer large hierarchical networks and interconnect developmental programs with secondary
metabolism triggered by chemical, oxidative,
light, or temperature sensing and subsequent
signal transduction pathways (Bayram et al.
2008b; Bayram and Braus 2012; Lind et al.
2016).
1. Chemical Sensing and Oxidative Stress as
Developmental Signal: How Fungi Smell
Their Environment
Chemical sensing is accomplished by G
protein-coupled receptors (GPCRs) with a common seven transmembrane domain architecture that initiate signal transduction through
binding to the heterotrimeric Ga, Gb, and Gg
protein complex. In Aspergilli, three different
Ga, one Gb, and one Gg protein exist (de Vries
et al. 2017; Brown et al. 2018). GPRCs are the
largest fungal group of surface receptors
important for sensing of pheromones, nutrients, and host cells in pathogenic interactions.
For instance, the binding of a pheromone to the
receptor initiates GDP-GTP exchange on the Ga
protein that then dissociates from the bg dimer
and typically activates a three-step mitogenactivated protein (MAP) kinase cascade, which
finally changes transcription. The result of this
well conserved cascade in fungi is a cell cycle
arrest and the cellular fusion of both mating
partners (Bahn et al. 2007). Further, similar
sensing systems through G protein-coupled
receptors with different transcriptional outcomes exist for different macro- and micronutrients including glucose as main carbon energy
source. Glucose is sensed through the sugar
receptor Gpr1 (G protein-coupled receptor 1)
that stimulates Gpa2 resulting in increased
cyclic adenosine monophosphate (cAMP) levels
through activation of adenylyl cyclase and protein kinase A (PKA). Active PKA inhibits the
Atg1 (autophagy-specific gene 1) initiation
kinase of autophagy degradation pathways
(see Sect. V.B). Specialized sugar transporters
such as yeast Snf3 (sucrose nonfermenting 3)
and Rgt2 (restores glucose transport 2) act as
sensors inducing signal transduction and
changed transcription (Bahn et al. 2007).
The regulation of the mycotoxin sterigmatocystin in A. nidulans works through a GaPKA pathway. The Ga protein FadA (fluffy
autolytic dominant A) activates PkaA (protein
kinase A A), which in turn is a repressor of the
specific transcription factor of the sterigmatocystin biosynthesis cluster, AflR (aflatoxin regulator). The activation of the Ga protein FadA
is inhibited by the fluffy low brlA protein FlbA
(Shimizu et al. 2003; Fig. 8.2).
Reactive oxygen species (ROS) function as
signalling molecules in light perception and
redox biology and thereby induce fungal development (Gessler et al. 2007). Therefore, an
impact on ROS homeostasis is often linked to
distorted development in filamentous fungi
(Nahlik et al. 2010; Kolog Gulko et al. 2018).
Fungi respond to oxidative stress induced by
ROS through activation of a MAP kinase pathway (Yu and Fischer 2019). The MAP kinase
Hog1 (high osmolarity glycerol response 1) of S.
cerevisiae or its homologue SakA (stress activated kinase A) in A. nidulans are activated by
ROS and in turn induce transcription factors
needed for the induction of the oxidative stress
response, such as the A. nidulans AtfA (activating transcription factor A). These transcription
factors regulate different antioxidants, such as
superoxide dismutases, catalases, peroxidases,
glutathione peroxidases, peroxiredoxins, and
antioxidative secondary metabolites. The
stress-activated kinase SakA is not only
induced by ROS but also by light, mediated
through the red light photoreceptor FphA (fungal phytochrome A), which represses fruiting
body formation in A. nidulans (Yu and Fischer
2019). SakA additionally mediates repression of
the A. nidulans NADPH oxidase gene noxA,
which is essential for different steps during
sexual fruiting body formation (Lara-Ortı ´z
et al. 2003).
8 Coordination of Fungal Secondary Metabolism and Development
179