factor. In contrast, A. flavus decreased spore
production but increased aflatoxin production
when exposed to R. solanacearum VOCs (Spraker et al. 2014). This highlights not only the
diverse patterns of VOCs but also the very specific “scent” fungi and their interactions seem
to have.
Even though no novel fungal SMs have been
identified thus far through methods involving
VOCs, it is conceivable that this approach will
become a valid strategy for silent SM gene cluster induction in the future.
4. Induction of Silent Natural Product Gene
Clusters by Co-cultivation of Fungi with
Non-microorganisms
Co-cultivation approaches need not be limited
to confrontations of microorganisms. This has
been elegantly demonstrated in a co-cultivation
experiment of Trichoderma harzianum and callus of the Madagascar periwinkle, Catharanthus
roseus, leading to the discovery of a novel fungal metabolite, trichosetin. This previously
undescribed tetramic acid exhibits remarkable
anti-Gram-positive activity also against MRSA
strains (Marfori et al. 2002).
B. Discovery of Fungal Natural Products
Inspired by Ecological Interactions
1. Natural Products from Fungi in Association
with Marine Organisms
Finding novel metabolites from fungi can be
achieved by exploring previously underinvestigated habitats and ecosystems. The sea is one
of these ecosystems, gaining increasing attention in screening for potential pharmaceutically
relevant compounds; indeed, a number of antibacterial natural products have been discovered this way [recently reviewed in (Blunt
et al. 2018)]. An early report describes the production of the chlorinated benzophenone antibiotic pestalone with potent anti-Gram-positive
activity by a fungus of the genus Pestalotia.
This fungus was originally isolated from the
surface of the marine alga Rosenvingea sp. and
only produced pestalone when co-cultured with
an unidentified unicellular marine bacterium
(Cueto et al. 2001).
Similarly, three novel chlorinated benzophenones, as
well as four novel natural products, pestaloisocoumarins A and B, isopolisin B and pestalotiol A were isolated
from the sponge-derived fungus Pestalotiopsis heterocornis. The chlorinated benzophenones as well as pestaloisocoumarins A and B exhibited potent anti-Grampositive activity (Lei et al. 2017).
GKK1032B and secalonic acid A were
isolated from the marine sponge-associated
fungus Penicillium erubescens and showed
activity against Gram-positive bacteria and in
the case of secalonic acid A also against MRSA
(Kumla et al. 2018). A marine A. fumigatus
strain, found in association with a sponge, was
able to produce seven novel antibacterial helvolic acid derivatives with potent activity
against the human and fish pathogenic bacterium Streptococcus agalactiae (Kong et al.
2018). Not only antibacterial natural products
were discovered by sampling fungi from marine
backgrounds. An A. fumigatus isolate from the
gastrointestinal tract of the marine fish Pseudolabrus japonicus produced seven cytotoxic
compounds, the fumiquinazolines A-G, when
cultured in artificial sea water for 3 weeks
(Takahashi et al. 1995). Liu et al. (2018) discovered three cyclic peptides from the spongederived Aspergillus violaceofuscus.
Among these compounds, a cyclic tetrapeptide, as
well as a diketopiperazine dimer exhibited antiinflammatory activity against interleukin-10 expression
of lipopolysaccharide-induced THP-1 cells.
Another isolate from a marine sponge is the
ascomycete Truncatella angustata, which produced 22 isoprenylated cyclohexanols on solid
medium. The novel derivative truncateol O
inhibited HIV-1 and H 1 N 1 viruses, while truncateol P exhibited activity against HIV-1 (Zhao
et al. 2018). Marine habitats and fungi in association with marine organisms like algae and
sponges can be regarded as a valuable source of
novel natural products with various pharmaceutically relevant features.
280
M. Flak et al.
production but increased aflatoxin production
when exposed to R. solanacearum VOCs (Spraker et al. 2014). This highlights not only the
diverse patterns of VOCs but also the very specific “scent” fungi and their interactions seem
to have.
Even though no novel fungal SMs have been
identified thus far through methods involving
VOCs, it is conceivable that this approach will
become a valid strategy for silent SM gene cluster induction in the future.
4. Induction of Silent Natural Product Gene
Clusters by Co-cultivation of Fungi with
Non-microorganisms
Co-cultivation approaches need not be limited
to confrontations of microorganisms. This has
been elegantly demonstrated in a co-cultivation
experiment of Trichoderma harzianum and callus of the Madagascar periwinkle, Catharanthus
roseus, leading to the discovery of a novel fungal metabolite, trichosetin. This previously
undescribed tetramic acid exhibits remarkable
anti-Gram-positive activity also against MRSA
strains (Marfori et al. 2002).
B. Discovery of Fungal Natural Products
Inspired by Ecological Interactions
1. Natural Products from Fungi in Association
with Marine Organisms
Finding novel metabolites from fungi can be
achieved by exploring previously underinvestigated habitats and ecosystems. The sea is one
of these ecosystems, gaining increasing attention in screening for potential pharmaceutically
relevant compounds; indeed, a number of antibacterial natural products have been discovered this way [recently reviewed in (Blunt
et al. 2018)]. An early report describes the production of the chlorinated benzophenone antibiotic pestalone with potent anti-Gram-positive
activity by a fungus of the genus Pestalotia.
This fungus was originally isolated from the
surface of the marine alga Rosenvingea sp. and
only produced pestalone when co-cultured with
an unidentified unicellular marine bacterium
(Cueto et al. 2001).
Similarly, three novel chlorinated benzophenones, as
well as four novel natural products, pestaloisocoumarins A and B, isopolisin B and pestalotiol A were isolated
from the sponge-derived fungus Pestalotiopsis heterocornis. The chlorinated benzophenones as well as pestaloisocoumarins A and B exhibited potent anti-Grampositive activity (Lei et al. 2017).
GKK1032B and secalonic acid A were
isolated from the marine sponge-associated
fungus Penicillium erubescens and showed
activity against Gram-positive bacteria and in
the case of secalonic acid A also against MRSA
(Kumla et al. 2018). A marine A. fumigatus
strain, found in association with a sponge, was
able to produce seven novel antibacterial helvolic acid derivatives with potent activity
against the human and fish pathogenic bacterium Streptococcus agalactiae (Kong et al.
2018). Not only antibacterial natural products
were discovered by sampling fungi from marine
backgrounds. An A. fumigatus isolate from the
gastrointestinal tract of the marine fish Pseudolabrus japonicus produced seven cytotoxic
compounds, the fumiquinazolines A-G, when
cultured in artificial sea water for 3 weeks
(Takahashi et al. 1995). Liu et al. (2018) discovered three cyclic peptides from the spongederived Aspergillus violaceofuscus.
Among these compounds, a cyclic tetrapeptide, as
well as a diketopiperazine dimer exhibited antiinflammatory activity against interleukin-10 expression
of lipopolysaccharide-induced THP-1 cells.
Another isolate from a marine sponge is the
ascomycete Truncatella angustata, which produced 22 isoprenylated cyclohexanols on solid
medium. The novel derivative truncateol O
inhibited HIV-1 and H 1 N 1 viruses, while truncateol P exhibited activity against HIV-1 (Zhao
et al. 2018). Marine habitats and fungi in association with marine organisms like algae and
sponges can be regarded as a valuable source of
novel natural products with various pharmaceutically relevant features.
280
M. Flak et al.