Novel SMs from fungal-fungal interaction
are not limited to antifungal activity: there are
also reports about production of antibacterial
compounds. The citrifelins A and B, citrinine
derivatives with a unique tetracyclic backbone,
were isolated from the culture broth of a coculture of marine-derived isolates of Penicillium citrinum and Beauveria feline (Meng
et al. 2015). Another example for metabolites
identified in co-cultures involving fungi of the
genus Penicillium are the berkeleylactones.
P. fuscum co-cultured with P. camembertii/clavigerum
yielded eight berkeleylactone derivatives.
Interestingly, these show a very high antimicrobial activity against Gram-positive bacteria such as MRSA, as well as the opportunistic
fungal pathogen Candida albicans. However,
unlike other macrolide antibiotics resembling
berkeleylactones, they do not interfere with
protein biosynthesis, indicating a novel mode
of action (Stierle et al. 2017).
Furthermore, the antibacterial alkaloid aspergicin was
produced, when two epiphytic Aspergillus sp. strains
were co-cultured (Zhu et al. 2011, 2017).
Another interesting instance of fungal cocultivation is that of two developmental stages
of Aspergillus alliaceus with one another. In this
fungus, the vegetative, asexual anamorph can
be separated from the sclerotia-forming morph
that induced sexual development. Both morphotypes produce distinct natural products
when grown in monoculture. Ochratoxin, a
potent mycotoxin, is being produced mainly
by the sexual teleomorph, while nalgiovensin,
an anthraquinone pigment, was produced by
the asexual stage. However, the natural product
pattern changed remarkably, when the asexual
and the sexual morph were co-cultivated. The
chlorinated nalgiovensin derivative, nalgiolaxin, increased in abundance, and weakly cytotoxic allianthrones A, B and C, novel natural
products, were produced (Mandelare et al.
2018). This example illustrates that not only
different species of fungi, but different developmental stages of the same strain, can interact
with each other and lead to different natural
product formation.
3. Induction of Fungal Volatile Compounds and
Their Role in Co-cultivation
Volatile organic compounds (VOCs) are generally considered to be small ( 20 C atoms),
possessing low molecular mass, high vapor
pressure, and a low boiling point. These characteristics enable easy transfer of VOCs in soil
and aboveground, which suggests that these
compounds serve as long-distance messengers
(Schmidt and Podmore 2015). Extensive
research was conducted investigating the role
of VOCs in communication of microorganisms
with their surroundings (Piechulla & Degenhardt 2014). As described below, there is now
growing evidence that VOCs also play an
important role in communication, signaling,
and growth inhibition of fungi, impacting
their physiological state, as well as secondary
metabolism. Evans et al. (2008) investigated the
production and influence of VOCs when various fungi where challenged with each other.
The VOC profiles were species-specific and
showed variation over time. Notably, the VOC
pattern generally changed when the fungi
were in contact with other fungi. Among a
number of other VOCs, a potentially antifungal
quinolinium-like compound was formed when
Hypholoma fasciculare was either self-paired or
co-cultivated with Trametes versicolor.
A similar approach was pursued when the gas phase of
the plant pathogens Eutypa lata and Botryosphaeria
obtusa were connected. The produced VOCs were
species-specific, variable over time, and subject to
change when fungal partners were in contact. One of
the detected VOCs, antifungal 2-nonanone, gradually
increased in abundance during co-cultivation. However, both fungi, i.e. including the producer strain,
were susceptible to the antifungal activity of 2nonanone (Azzollini et al. 2018).
There is also a specific volatome response
between two peanut pathogens Aspergillus flavus and Ralstonia solanacearum. A. flavus
VOCs reduced the production of exopolysaccharides, R. solanacearum’s major virulence
11 New Avenues Toward Drug Discovery in Fungi
279
are not limited to antifungal activity: there are
also reports about production of antibacterial
compounds. The citrifelins A and B, citrinine
derivatives with a unique tetracyclic backbone,
were isolated from the culture broth of a coculture of marine-derived isolates of Penicillium citrinum and Beauveria feline (Meng
et al. 2015). Another example for metabolites
identified in co-cultures involving fungi of the
genus Penicillium are the berkeleylactones.
P. fuscum co-cultured with P. camembertii/clavigerum
yielded eight berkeleylactone derivatives.
Interestingly, these show a very high antimicrobial activity against Gram-positive bacteria such as MRSA, as well as the opportunistic
fungal pathogen Candida albicans. However,
unlike other macrolide antibiotics resembling
berkeleylactones, they do not interfere with
protein biosynthesis, indicating a novel mode
of action (Stierle et al. 2017).
Furthermore, the antibacterial alkaloid aspergicin was
produced, when two epiphytic Aspergillus sp. strains
were co-cultured (Zhu et al. 2011, 2017).
Another interesting instance of fungal cocultivation is that of two developmental stages
of Aspergillus alliaceus with one another. In this
fungus, the vegetative, asexual anamorph can
be separated from the sclerotia-forming morph
that induced sexual development. Both morphotypes produce distinct natural products
when grown in monoculture. Ochratoxin, a
potent mycotoxin, is being produced mainly
by the sexual teleomorph, while nalgiovensin,
an anthraquinone pigment, was produced by
the asexual stage. However, the natural product
pattern changed remarkably, when the asexual
and the sexual morph were co-cultivated. The
chlorinated nalgiovensin derivative, nalgiolaxin, increased in abundance, and weakly cytotoxic allianthrones A, B and C, novel natural
products, were produced (Mandelare et al.
2018). This example illustrates that not only
different species of fungi, but different developmental stages of the same strain, can interact
with each other and lead to different natural
product formation.
3. Induction of Fungal Volatile Compounds and
Their Role in Co-cultivation
Volatile organic compounds (VOCs) are generally considered to be small ( 20 C atoms),
possessing low molecular mass, high vapor
pressure, and a low boiling point. These characteristics enable easy transfer of VOCs in soil
and aboveground, which suggests that these
compounds serve as long-distance messengers
(Schmidt and Podmore 2015). Extensive
research was conducted investigating the role
of VOCs in communication of microorganisms
with their surroundings (Piechulla & Degenhardt 2014). As described below, there is now
growing evidence that VOCs also play an
important role in communication, signaling,
and growth inhibition of fungi, impacting
their physiological state, as well as secondary
metabolism. Evans et al. (2008) investigated the
production and influence of VOCs when various fungi where challenged with each other.
The VOC profiles were species-specific and
showed variation over time. Notably, the VOC
pattern generally changed when the fungi
were in contact with other fungi. Among a
number of other VOCs, a potentially antifungal
quinolinium-like compound was formed when
Hypholoma fasciculare was either self-paired or
co-cultivated with Trametes versicolor.
A similar approach was pursued when the gas phase of
the plant pathogens Eutypa lata and Botryosphaeria
obtusa were connected. The produced VOCs were
species-specific, variable over time, and subject to
change when fungal partners were in contact. One of
the detected VOCs, antifungal 2-nonanone, gradually
increased in abundance during co-cultivation. However, both fungi, i.e. including the producer strain,
were susceptible to the antifungal activity of 2nonanone (Azzollini et al. 2018).
There is also a specific volatome response
between two peanut pathogens Aspergillus flavus and Ralstonia solanacearum. A. flavus
VOCs reduced the production of exopolysaccharides, R. solanacearum’s major virulence
11 New Avenues Toward Drug Discovery in Fungi
279