There are also quite recent examples of
novel fungal natural products discovered by
studying fungal-bacterial interactions. A
marine isolate of A. fumigatus produced the
undiscovered luteoride D, along with pseurotin
G, 11-O-methylpseurotin, and terezine D, when
co-cultured with two desert-derived strains of
Streptomyces leeuwenhoekii (Wakefield et al.
2017).
Expectedly, the effect of activation of silent
metabolic clusters in fungi is not limited
to streptomycetes. Abdelwahab et al. (2018)
described the production of aspvanicin A and
its epimer aspvanicin B in co-culture of Aspergillus versicolor with Bacillus subtilis.
Aspvanicin B shows anti-proliferative activity towards
mouse lymphoma cell lines.
Similarly, Aspergillus is not the only fungal
genus useful for co-cultivation approaches.
In the co-culture of an endophytic fungus Trichoderma sp. with Acinetobacter johnsonii,
two previously undescribed sesquiterpenes,
namely, microsphaeropsisin B and C, and two
new de-O-methyllasiodiplodins were detected
(Zhang et al. 2017).
In addition to the novel compounds, these cocultivations yielded 12 known products.
Basidiomycetes are also capable of adjusting their secondary metabolism in interaction
with bacteria. The brown rot fungus Serpula
lacrymans shows production of pigmented
non-ribosomal peptides when in contact with
one of at least 13 different bacteria, but not in
monoculture. Among these colored compounds, variegatic acid and xerocomic acid
decreased swarming and biofilm formation of
B. subtilis by a potentially novel, nontoxic mode
of action (Tauber et al. 2016, 2018). Streptomyces AcH 505 induced the formation of a 5formylsalicylic acid (5-FSA) in the plant pathogenic basidiomycete Heterobasidion abietinum.
The addition of this compound to H. abietinum infecting Norway spruce seedlings led to increased detrimental effects to the plant and an elevation of fungal
biomass. However, 5-FSA alone added to the plant did
not inhibit plant growth (Keilhofer et al. 2018). This
leads to the assumption that the streptomycete helps
the fungus to infect the host plant by production of a
natural product.
Taken together, bacterial-fungal cocultivation has been highly successful in discovery of novel natural products and might
also be used to shed light on their role in the
natural habitats of the producing organisms.
2. Induction of Silent Secondary Metabolite
Gene Clusters by Co-cultivation of Fungi
with Other Fungi
In accordance with the idea that co-cultivation
of fungi with bacteria might result in the induction of otherwise silent natural product biosynthetic gene clusters, there are successful
approaches of co-cultivation of one fungal species with another that yield novel secondary
metabolites with antifungal properties. Three
novel lipoaminopeptides, the acremostatins A,
B, and C, were discovered when the endophytic
ascomycete Acremonium sp. and the mycoparasite Mycogone rosea were cultivated together
(Degenkolb et al. 2002).
These SMs bear structural resemblance to leucinostatins, which show activity against the major potato pathogen Phytophtora infestans (Wang et al. 2016a).
Antifungal natural products are also
formed when isolates of Phomopsis sp. and
Alternaria sp. are co-cultured. Li et al. (2014)
reported the production of a new cyclic tetrapeptide in mixed fermentation. Interestingly,
the newly discovered natural product shows
promising activity against several plant pathogenic fungi (Li et al. 2014). The co-cultivation of
the two mollusk-derived fungi, Chaunopycnis
sp. and Trichoderma hamatum, is an interesting showcase for multi-level fungal interactions. Chaunopycnis sp. was shown to not only
produce the novel natural product chaunopyran A but also biotransform pyridoxatin produced by Trichoderma hamatum to methylpyridoxatin, deactivating the molecule’s antifungal properties (Shang et al. 2017).
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M. Flak et al.
novel fungal natural products discovered by
studying fungal-bacterial interactions. A
marine isolate of A. fumigatus produced the
undiscovered luteoride D, along with pseurotin
G, 11-O-methylpseurotin, and terezine D, when
co-cultured with two desert-derived strains of
Streptomyces leeuwenhoekii (Wakefield et al.
2017).
Expectedly, the effect of activation of silent
metabolic clusters in fungi is not limited
to streptomycetes. Abdelwahab et al. (2018)
described the production of aspvanicin A and
its epimer aspvanicin B in co-culture of Aspergillus versicolor with Bacillus subtilis.
Aspvanicin B shows anti-proliferative activity towards
mouse lymphoma cell lines.
Similarly, Aspergillus is not the only fungal
genus useful for co-cultivation approaches.
In the co-culture of an endophytic fungus Trichoderma sp. with Acinetobacter johnsonii,
two previously undescribed sesquiterpenes,
namely, microsphaeropsisin B and C, and two
new de-O-methyllasiodiplodins were detected
(Zhang et al. 2017).
In addition to the novel compounds, these cocultivations yielded 12 known products.
Basidiomycetes are also capable of adjusting their secondary metabolism in interaction
with bacteria. The brown rot fungus Serpula
lacrymans shows production of pigmented
non-ribosomal peptides when in contact with
one of at least 13 different bacteria, but not in
monoculture. Among these colored compounds, variegatic acid and xerocomic acid
decreased swarming and biofilm formation of
B. subtilis by a potentially novel, nontoxic mode
of action (Tauber et al. 2016, 2018). Streptomyces AcH 505 induced the formation of a 5formylsalicylic acid (5-FSA) in the plant pathogenic basidiomycete Heterobasidion abietinum.
The addition of this compound to H. abietinum infecting Norway spruce seedlings led to increased detrimental effects to the plant and an elevation of fungal
biomass. However, 5-FSA alone added to the plant did
not inhibit plant growth (Keilhofer et al. 2018). This
leads to the assumption that the streptomycete helps
the fungus to infect the host plant by production of a
natural product.
Taken together, bacterial-fungal cocultivation has been highly successful in discovery of novel natural products and might
also be used to shed light on their role in the
natural habitats of the producing organisms.
2. Induction of Silent Secondary Metabolite
Gene Clusters by Co-cultivation of Fungi
with Other Fungi
In accordance with the idea that co-cultivation
of fungi with bacteria might result in the induction of otherwise silent natural product biosynthetic gene clusters, there are successful
approaches of co-cultivation of one fungal species with another that yield novel secondary
metabolites with antifungal properties. Three
novel lipoaminopeptides, the acremostatins A,
B, and C, were discovered when the endophytic
ascomycete Acremonium sp. and the mycoparasite Mycogone rosea were cultivated together
(Degenkolb et al. 2002).
These SMs bear structural resemblance to leucinostatins, which show activity against the major potato pathogen Phytophtora infestans (Wang et al. 2016a).
Antifungal natural products are also
formed when isolates of Phomopsis sp. and
Alternaria sp. are co-cultured. Li et al. (2014)
reported the production of a new cyclic tetrapeptide in mixed fermentation. Interestingly,
the newly discovered natural product shows
promising activity against several plant pathogenic fungi (Li et al. 2014). The co-cultivation of
the two mollusk-derived fungi, Chaunopycnis
sp. and Trichoderma hamatum, is an interesting showcase for multi-level fungal interactions. Chaunopycnis sp. was shown to not only
produce the novel natural product chaunopyran A but also biotransform pyridoxatin produced by Trichoderma hamatum to methylpyridoxatin, deactivating the molecule’s antifungal properties (Shang et al. 2017).
278
M. Flak et al.