Endophytes are microbes that inhabit host plants without causing disease and are reported to be reservoirs of metabolites that combat microbes and other pathogens. Here we review diverse classes of secondary metabolites, focusing on anti-microbial compounds, synthesized by fungal endophytes including terpenoids, alkaloids, phenylpropanoids, aliphatic compounds, polyketides, and peptides from the interdisciplinary perspectives of biochemistry, genetics, fungal biology, host plant biology, human and plant pathology. Several trends were apparent. First, host plants are often investigated for endophytes when there is prior indigenous knowledge concerning human medicinal uses (e.g., Chinese herbs). However, within their native ecosystems, and where investigated, endophytes were shown to produce compounds that target pathogens of the host plant. In a few examples, both fungal endophytes and their hosts were reported to produce the same compounds. Terpenoids and polyketides are the most purified anti-microbial secondary metabolites from endophytes, while flavonoids and lignans are rare. Examples are provided where fungal genes encoding anti-microbial compounds are clustered on chromosomes. As different genera of fungi can produce the same metabolite, genetic clustering may facilitate sharing of anti-microbial secondary metabolites between fungi. We discuss gaps in the literature and how more interdisciplinary research may lead to new opportunities to develop bio-based commercial products to combat global crop and human pathogens.

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The diversity of anti-microbial secondary metabolites produced by fungal endophytes: an interdisciplinary perspective

Important fungi growing on cheese include Penicillium, Aspergillus, Cladosporium, Geotrichum, Mucor, and Trichoderma. For some cheeses, such as Camembert, Roquefort, molds are intentionally added. However, some contaminating or technological fungal species have the potential to produce undesirable metabolites such as mycotoxins. The most hazardous mycotoxins found in cheese, ochratoxin A and aflatoxin M1, are produced by unwanted fungal species either via direct cheese contamination or indirect milk contamination (animal feed contamination), respectively. To date, no human food poisoning cases have been associated with contaminated cheese consumption. However, although some studies state that cheese is an unfavorable matrix for mycotoxin production; these metabolites are actually detected in cheeses at various concentrations. In this context, questions can be raised concerning mycotoxin production in cheese, the biotic and abiotic factors influencing their production, mycotoxin relative toxicity as well as the methods used for detection and quantification. This review emphasizes future challenges that need to be addressed by the scientific community, fungal culture manufacturers, and artisanal and industrial cheese producers.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1541-4337.12069

Filamentous Fungi and Mycotoxins in Cheese: A Review

Secondary metabolites produced by Penicillium paneum and Penicillium roqueforti from baled grass silage were analyzed. A total of 157 isolates were investigated, comprising 78 P. paneum and 79 P. roqueforti isolates randomly selected from more than 900 colonies cultured from bales. The findings mostly agreed with the literature, although some metabolites were not consistently produced by either fungus. Roquefortine C, marcfortine A, and andrastin A were consistently produced, whereas PR toxin and patulin were not. Five silage samples were screened for fungal metabolites, with two visually moldy samples containing up to 20 mg/kg of roquefortine C, mycophenolic acid, and andrastin A along with minor quantities (0.1-5 mg/kg) of roquefortines A, B, and D, festuclavine, marcfortine A, and agroclavine. Three visually nonmoldy samples contained low amounts of mycophenolic acid and andrastin A. The ability of both molds to produce a diverse range of secondary metabolites in vitro and in silage should be a concern to livestock producers.

https://orbit.dtu.dk/files/2986500/kristian.pdf

Mycotoxins and other secondary metabolites produced in vitro by Penicillium paneum Frisvad and Penicillium roqueforti Thom isolated from baled grass silage in Ireland.

Publisher Summary This chapter discusses the mode of action of mycotoxins and related compounds. Mycotoxin is a convenient generic term to describe the toxic substances formed during the growth of fungi. In contrast to the bacterial toxins which are mainly proteins with antigenic properties, the mycotoxins encompass a considerable variety of fungal secondary metabolites with diverse chemical structures and biological activities. In considering the effect of mycotoxins on the animal's body, it is important to distinguish between “mycotoxicosis” and “mycosis.” Mycotoxicosis is used, in general, to describe the action of mycotoxin(s) and is frequently mediated through a number of organs, notably the liver, kidney, lung, and nervous system. On the other hand, mycosis refers to a generalized invasion of living tissue(s) by growing fungi. Mycotoxins and mycotoxicosis are an especially significant problem for human and animal health, because under certain conditions, foodstuffs can provide a favorable medium for fungus growth and toxin production.

Mode of action of mycotoxins and related compounds.

Roquefortine C occurrence in blue cheese.

Mechanism of the inhibition of transcription by pr toxin, a mycotoxin from penicillium roqueforti

It is currently accepted that the base composition of the RNA synthesized in vitro by RNA polymerase of rat liver nuclei, depends on both the nature of the cation added to the incubation medium and the ionic strength of this medium. However, up to the present time, the foregoing results have been obtained on nuclei isolated in sucrose solution containing Mg2+ (1 to 3 mM). The influence of the isolation medium of nuclei has so far never been considered.



The present results demonstrate that the ratio A/G of the RNA synthesized in vitro is much more determined by the cation added to the isolation medium than that present in the incubation assay. Nuclei isolated either in the presence of 1 mM Mn2+ or in the absence of cation added to sucrose solution synthesize (at low ionic strength) RNA molecules with a ratio A/G 1 regardless of the ion present in the standard assay. Thus, presence of Mg2+ during the isolation of nuclei appears to suppress their ability to transcribe in vitro DNA-like RNA although allowing an optimal synthesis of ribosomal RNA.



The properties of liver nuclei isolated in various conditions have been studied in relation to their transcriptional ability, and the results have been discussed taking into account the different possibilities of action of the cations upon the nucleus.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1970.tb01199.x

N. Rousseau

Papers

Mechanism of the inhibition of transcription by pr toxin, a mycotoxin from penicillium roqueforti

The Effects of Magnesium and Manganese on the Purine Ratio of RNA Transcribed in vitro by Rat Liver Nuclei

Action of monovalent cations on the biological properties of PR toxin, a mycotoxin from Penicillium roqueforti