ium, Penicillium, Trichoderma, and Aspergillus
(Bok and Keller 2016). Absence of laeA or overexpression of mcrA results in silencing, whereas
laeA overexpression or mcrA deletion leads to
increased production of several secondary
metabolites (Bok and Keller 2016; Oakley et al.
2016). The fact that only some global regulators
are conserved, whereas the targets of individual
regulators differ considerably, correlates with
the finding that secondary metabolite genes
are more variable and significantly less conserved than genes of the primary metabolism
(Lind et al. 2015).
2. The Fungal Velvet Complex Physically
Connects Transcriptional and
Heterochromatin Control to Coordinate
Secondary Metabolism and Development
Velvet proteins with their characteristic velvet
domain, such as VeA (velvet A), VelB (velvetlike B) VelC (velvet-like C), and VosA in A.
nidulans, form complex regulatory networks
by direct DNA binding to thousands of target
gene promoters in numerous fungi (Ahmed
et al. 2013; Becker et al. 2016; Fig. 8.2). The
master regulator of secondary metabolism
LaeA is physically linked to the heterodimer
VeA-VelB to coordinate secondary metabolite
biosynthesis with developmental programs. It
was originally shown in A. nidulans that this
VelB-VeA-LaeA complex is required for the
appropriate formation of fruiting bodies and
concomitant production of the aflatoxin family
metabolite sterigmatocystin (Bayram et al.
2008b). LaeA is a methyltransferase and acts
as epigenetic control element by counteracting
the silencing heterochromatic lysine 9 methylation marks at histone H3 in secondary metabolite clusters (Strauss and Reyes-Dominguez
2011; see Sect. III.A). VeA, which provides the
interphase of the trimeric complex, therefore
physically links transcription to posttranslational epigenetic control of histone modifications (Sarikaya-Bayram et al. 2015). Velvet
proteins and LaeA contribute to the virulence
of several fungi, possibly through mycotoxin
production (Wiemann et al. 2010; Kumar et al.
2016; Lo ´pez-Dı ´az et al. 2018). The trimeric velvet complex is conserved in the fungal kingdom
and can physically interact through VeA with
the phytochrome FphA as part of the light and
presumably temperature control machinery
(Lind et al. 2016; Yu and Fischer 2019). The
light reception through VeA-FphA-LreA-LreB
is presumably less stable and rather transient
in comparison to the velvet complex VelB-VeALaeA (Bayram et al. 2010).
3. Velvet Domain Transcription Factors
Expand Their Transcriptional Networks
Through Formation of Sub-networks
Velvet domain proteins control several genetic
networks either acting as homo- or heterodimers (Fig. 8.2). VelB does not only support as
VelB-VeA heterodimer sexual development
linked to its specific secondary metabolism
but also represses asexual development in combination with the velvet protein VosA as VelBVosA together with VosA-VosA (Park and Yu
2012). Additionally, VelB-VosA is a positive
regulator for spore viability (Park and Yu
2012). How the formation of the different
VosA complexes is regulated is still unknown.
Velvet proteins bind to promoters of hundreds
of genes, including genes for additional transcription factors, which in turn control their
own genetic network (Ahmed et al. 2013).
VosA directly represses the central asexual
regulator gene brlA and the gene for the
Zn 2 Cys 6 zinc cluster domain transcriptional
activator SclB. The SclB network induces early
developmental genes including brlA to promote
asexual sporulation and to support spore viability. SclB links asexual spore formation to its
specific secondary metabolism, including the
putative signal molecule dehydroaustinol, and
to the fungal oxidative stress response (Thieme
et al. 2018). This illustrates a convoluted surveillance apparatus, including sub-networks
with feedback mechanisms and overlapping as
well as antagonistic functions, to perform fungal development and its accurate linkage to the
appropriate secondary metabolism (Fig. 8.2).
Developmental functions of velvet domain proteins are rewired in different fungi. Whereas
veA is dispensable for conidiation in A. nidu8 Coordination of Fungal Secondary Metabolism and Development
183
(Bok and Keller 2016). Absence of laeA or overexpression of mcrA results in silencing, whereas
laeA overexpression or mcrA deletion leads to
increased production of several secondary
metabolites (Bok and Keller 2016; Oakley et al.
2016). The fact that only some global regulators
are conserved, whereas the targets of individual
regulators differ considerably, correlates with
the finding that secondary metabolite genes
are more variable and significantly less conserved than genes of the primary metabolism
(Lind et al. 2015).
2. The Fungal Velvet Complex Physically
Connects Transcriptional and
Heterochromatin Control to Coordinate
Secondary Metabolism and Development
Velvet proteins with their characteristic velvet
domain, such as VeA (velvet A), VelB (velvetlike B) VelC (velvet-like C), and VosA in A.
nidulans, form complex regulatory networks
by direct DNA binding to thousands of target
gene promoters in numerous fungi (Ahmed
et al. 2013; Becker et al. 2016; Fig. 8.2). The
master regulator of secondary metabolism
LaeA is physically linked to the heterodimer
VeA-VelB to coordinate secondary metabolite
biosynthesis with developmental programs. It
was originally shown in A. nidulans that this
VelB-VeA-LaeA complex is required for the
appropriate formation of fruiting bodies and
concomitant production of the aflatoxin family
metabolite sterigmatocystin (Bayram et al.
2008b). LaeA is a methyltransferase and acts
as epigenetic control element by counteracting
the silencing heterochromatic lysine 9 methylation marks at histone H3 in secondary metabolite clusters (Strauss and Reyes-Dominguez
2011; see Sect. III.A). VeA, which provides the
interphase of the trimeric complex, therefore
physically links transcription to posttranslational epigenetic control of histone modifications (Sarikaya-Bayram et al. 2015). Velvet
proteins and LaeA contribute to the virulence
of several fungi, possibly through mycotoxin
production (Wiemann et al. 2010; Kumar et al.
2016; Lo ´pez-Dı ´az et al. 2018). The trimeric velvet complex is conserved in the fungal kingdom
and can physically interact through VeA with
the phytochrome FphA as part of the light and
presumably temperature control machinery
(Lind et al. 2016; Yu and Fischer 2019). The
light reception through VeA-FphA-LreA-LreB
is presumably less stable and rather transient
in comparison to the velvet complex VelB-VeALaeA (Bayram et al. 2010).
3. Velvet Domain Transcription Factors
Expand Their Transcriptional Networks
Through Formation of Sub-networks
Velvet domain proteins control several genetic
networks either acting as homo- or heterodimers (Fig. 8.2). VelB does not only support as
VelB-VeA heterodimer sexual development
linked to its specific secondary metabolism
but also represses asexual development in combination with the velvet protein VosA as VelBVosA together with VosA-VosA (Park and Yu
2012). Additionally, VelB-VosA is a positive
regulator for spore viability (Park and Yu
2012). How the formation of the different
VosA complexes is regulated is still unknown.
Velvet proteins bind to promoters of hundreds
of genes, including genes for additional transcription factors, which in turn control their
own genetic network (Ahmed et al. 2013).
VosA directly represses the central asexual
regulator gene brlA and the gene for the
Zn 2 Cys 6 zinc cluster domain transcriptional
activator SclB. The SclB network induces early
developmental genes including brlA to promote
asexual sporulation and to support spore viability. SclB links asexual spore formation to its
specific secondary metabolism, including the
putative signal molecule dehydroaustinol, and
to the fungal oxidative stress response (Thieme
et al. 2018). This illustrates a convoluted surveillance apparatus, including sub-networks
with feedback mechanisms and overlapping as
well as antagonistic functions, to perform fungal development and its accurate linkage to the
appropriate secondary metabolism (Fig. 8.2).
Developmental functions of velvet domain proteins are rewired in different fungi. Whereas
veA is dispensable for conidiation in A. nidu8 Coordination of Fungal Secondary Metabolism and Development
183