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Chapter 54 : Biologically Active Secondary Metabolites from the Fungi

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Abstract:

Fungi, plants, and bacteria are the major kingdoms of life with well-developed secondary metabolism. About 500,000 secondary metabolites (also referred to as natural products) have been described to date. About 100,000 of these are derived from animals, 350,000 are from plants, and 70,000 are from microbes ( ). Roughly 33,500 bioactive microbial metabolites have been described ( ). Of these 33,500 microbial metabolites, about 12.5% (4,200) are metabolites of unicellular bacteria and cyanobacteria, 41% (13,700) are products of Actinomycete fermentations, and about 47% (15,600) are of fungal origin ( ). Furthermore, the rate of discovery of new fungal metabolites has accelerated significantly in the past two decades relative to the rate of discovery in the actinomycetes, filamentous bacteria that traditionally have been the richest source of microbial natural products ( ). This complex and rich secondary metabolism is highly developed in the filamentous Ascomycota and Basidiomycota, while it is underdeveloped in the unicellular forms of the Ascomycota and Basidiomycota and in the Zygomycota, Blastocladiomycota, and Chytridiomycota ( Fig. 1 ). The diversity of fungal species, particularly in the Ascomycota and Basidiomycota, and the accompanying diversification of biosynthetic genes and gene clusters points to an almost limitless potential for metabolic variation. In fact, one can argue that much of the ecological success of the filamentous fungi in colonizing virtually all habitats on the planet is owed to their ability to deploy arrays of secondary metabolites in concert with their penetrative and absorptive life forms. This dependence of the fungi on secondary metabolites to conquer diverse habitats and sustain their existence within them is evidenced by the facts that most species make multiple types of secondary metabolites, their expression is orchestrated with the life cycle and environment, and significant portions of their genomes are devoted to encoding and regulating the production of these products.

Citation: Bills G, Gloer J. 2017. Biologically Active Secondary Metabolites from the Fungi, p 1087-1119. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.FUNK-0009-2016
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Figure 1

Simplified phylogeny of the phyla and classes of the Fungi. Numbers after phylum or class indicate the average number of secondary metabolite, transport, and catabolism genes recognized by the Clusters of Orthologous Groups of Proteins Classification (KOGs) from sequenced genomes (number in parentheses) of fungi at the Joint Genome Institute’s Mycosm Project (January 15, 2016). Taxa shaded in gray are known to produce secondary metabolites with high frequency. Branch length reflects relatedness of taxa.

Citation: Bills G, Gloer J. 2017. Biologically Active Secondary Metabolites from the Fungi, p 1087-1119. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.FUNK-0009-2016
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Figure 2

Structures of mycophenolic acid and gibberellic acid.

Citation: Bills G, Gloer J. 2017. Biologically Active Secondary Metabolites from the Fungi, p 1087-1119. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.FUNK-0009-2016
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Figure 3

Some rudimentary fungal metabolites. Hadicidin. Cyclo (-leucine--proline). Cyclo (-proline--phenylalanine). Dipicolinic acid. -DOPA. Tyrosol. 3-Nitropropionic acid. Mycosporine serinol. Farnesol. Cordycepin. Kojic acid.

Citation: Bills G, Gloer J. 2017. Biologically Active Secondary Metabolites from the Fungi, p 1087-1119. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.FUNK-0009-2016
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Figure 4

Schematic representation of a cyclodipeptide synthase biosynthetic pathway. A cyclodipeptide synthase (red) binds aa-tRNAs (black) via a serine residue (Ser) to produce cyclodipeptides. aa-tRNAs are generated from an amino acid, ATP, and tRNAs.

Citation: Bills G, Gloer J. 2017. Biologically Active Secondary Metabolites from the Fungi, p 1087-1119. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.FUNK-0009-2016
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Figure 5

Some fungal metabolites derived from the shikimic acid pathway and ribosomally synthesized and posttranslationally modified peptides (RiPPs). Involutin. α-Amanitin. Phalloidin. Ustiloxin A. Phomopsin A. Epichloëcyclin A.

Citation: Bills G, Gloer J. 2017. Biologically Active Secondary Metabolites from the Fungi, p 1087-1119. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.FUNK-0009-2016
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Figure 6

Some fungal polyketides, nonribosomal peptides, and terpenoids. Griseofulvin. 6-Methyl salicylic acid. (R)-Mellein. Lovastatin. Cyclosporine A. Pneumocandin A. Pleuromutilin. Fusidic acid.

Citation: Bills G, Gloer J. 2017. Biologically Active Secondary Metabolites from the Fungi, p 1087-1119. In Heitman J, Howlett B, Crous P, Stukenbrock E, James T, Gow N (ed), The Fungal Kingdom. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.FUNK-0009-2016
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