Secondary Fungal Metabolites and Their Biological Activities, V. Investigations Concerning the Induction of the Biosynthesis of Toxic Secondary Metabolites in Basidiomycetes

Abstract

In cultures of the basidiomycetes Heterobasidion annosum, Gloeophyllum abietinum or Armillaria ostoyae, the biosynthesis of some of their toxic secondary metabolites is enhanced up to 400-fold when they grow in the presence of an antagonist. This stimulation is induced before any cell contact occurs. The "inducing signals" are not macromolecules, polypeptides or constituents of the cell membranes, but the same toxins which are synthesized already in monocultures in very low concentrations. After excretion and diffusion into the media, the fungi thus recognize the proximity of the antagonist in dualcultures. As a consequence, the enormous stimulation of toxin synthesis takes place. The increasing toxin concentrations in the fungal dual cultures finally cause the formation of mycel-free growth inhibition zones between the fungi, or sometimes one of the contrahents is killed. This stimulation of toxin synthesis is achieved by an enhanced de novo synthesis of enzymes of the corresponding secondary pathways.

Antibiotic dialogues: induction of silent biosynthetic gene clusters by exogenous small molecules

“…It would stand to reason then that systematic coculture screens could lead to new, perhaps cryptic, bioactive molecules that cannot be accessed otherwise. Early support for this idea came from Peipp and Sokolova (Iakovleva and Sokolova 1978;Sonnenbichler, Dietrich and Peipp 1994). Peipp, for example, found that constitutive, albeit low-level, production of a toxin by the fungus Heterobasidion annosum stimulated the biosynthesis of several toxins by a second fungus, Gloeophyllum abietinum, in liquid coculture.…”

“…Peipp, for example, found that constitutive, albeit low-level, production of a toxin by the fungus Heterobasidion annosum stimulated the biosynthesis of several toxins by a second fungus, Gloeophyllum abietinum, in liquid coculture. These overproduced toxins included oosponol (∼92-fold) and oospoglycol (∼14-fold) (Sonnenbichler, Dietrich and Peipp 1994). While numerous applications have followed, this method largely remains an underexplored strategy for the discovery of new and cryptic small molecules (Kolter and van Wezel 2016).…”

“…However, neither of these examples represents a methodical microbial coculture experiment. Testing of bacterial and fungal extracts against other bacteria continued for the following decades, but systematic coculture studies only became popular toward the end of the century (Iakovleva and Sokolova 1978;Sonnenbichler, Dietrich and Peipp 1994;Mearns-Spragg et al 1998;Ueda et al 2000). Broadly speaking, induction of silent gene clusters as a function of coculture can result from one of three interaction modes: (1) provision of nutrients, (2) competition via production of an antibiotic or a signaling molecule and (3) cell-cell contact.…”

The Effect of Aeration upon the Secondary Metabolism of Microorganisms

“…The process was unrelated to the presence of cell wall materials, as in fungal/plant interactions, and occurred before any cell contact had taken place (Sonnenbichler et al, 1994). For example, fomanosin and fomanoxin from Heterobasidion annosum were responseinducing metabolites.…”

In vitro interaction studies between Glomus intraradices and Armillaria mellea in vines

“…Hepper (1979) observed that the spore germination and the growth of AM fungal mycelium could be stimulated or inhibited by different compounds, and the production of toxic secondary metabolites by Armillaria sp. has been reported by several authors (Peipp and Sonnenbichler, 1992;Sonnenbichler et al, 1994). The release of these compounds, induced by the presence of antagonistic fungi and plant cells, can inhibit the growth of other microorganisms and even induce cell death before any contact occurs (Peipp and Sonnenbichler, 1992).…”