Secondary metabolites of fungi

1. Secondary metabolites of Fungi
Marlia Singgih Wibowo

2. Fungal secondary metabolites
• Secondary metabolites are compounds
produced by an organism that are not
required for primary metabolic processes.
Fungi produce an enormous array of
secondary metabolites, some of which are
important in industry

3. • Many fungi express secondary metabolites
that influence competitive outcomes.
• The compounds are expressed along with
enzymes necessary for extracellular digestion.
• The precise function of many of these
compounds in the natural environment,
however, is unclear.

4. • Secondary metabolites are generally
produced following active growth, and many
have an unusual chemical structure. Some
metabolites are found in a range of related
fungi, while others are only found in one or a
few species. The restricted distribution implies
a lack of general function of secondary
metabolites in fungi.

5. • six of the twenty most commonly prescribed
medications are of fungal origin. These
metabolites have been subjected to
combinatorial chemistry following growth in
selective media.
• Some metabolites are toxic to humans and
other animals. Yet others can modify the
growth and metabolism of plants.

6. The pathway
• Interestingly, the most important secondary
metabolites seem to be synthesised from one
or a combination of three biosynthetic
pathways: polyketides arising from Acetyl
Coenzyme A, mevalonate pathway that also
arises from Acetyl Coenzyme A, and from
amino acids.

7. • genes for the synthesis of some important
secondary metabolites are found clustered
together, and expression of the cluster
appears to be induced by one or a few global
regulators.

8. Polyketide Metabolites
• Polymerisation of acetate may result in the
formation of a fatty acid or a polyketide.
Polyketides result when a primer other than
acetate is included, and processing during
chain elongation results in the inclusion of
various other compounds. The chain may be
further processed by cyclisation, lactonisation,
or formation of thioesters or amides. The
result is a staggering number of possile
structures built from the simple primer units.

9. • Included among the polyketide secondary
metabolites are orsellinic acid,
tetrahydroxynaphthalene (precursor for
melanin), sterigmatocyctin, aflatoxins, statins,
and fumonisin.

10. Aflatoxin
• Aflatoxins are produced in members of the
Aspergillus parasiticus group via the
polyketide pathway. The pathway has around
20 steps, and the end products include a
diversity of related compounds
(bisfuranocoumarins) that can be readily
converted one to another.

11. • Aflatoxin B1 is one of the most toxic compounds
known. The toxin is formed commonly in plant
materials held at relatively high moisture and
temperature for long periods (ie growth in
tropics and sub‐tropics). Peanuts, corn and
cotton are readily contaminated in the field. The
Aspergillus parasiticus group of fungi are
common in soil. The fungi can colonise roots and
spread through the plant. When harvested,
contaminated seed will become toxic if not dried
immediately and held in a dry form.

12. Structure of Aflatoxin B1

13. • Aflatoxins are toxic and carcinogenic.
• The LSD 50 for ducks is 0.33 mg/kg. At lower
levels and following prolonged exposure, the
toxins cause liver cancer in humans.
• Aflatoxin B1 is converted to Aflatoxin M (in
milk) on passage through cows. Though less
toxic, it does illustrate the potential damage
caused by consumption of contaminated
product.

14. Aromatic Compounds
• Cyclic compounds can be synthesised via the
polyketide or shikimic acid pathways.
Zearalenone is one interesting example from
this group. The compound regulates
perithecium formation in the fungus. It also
has an oestrogenic effect in mammals.

15. Structure of Zearalenone

16. Amino Acid Pathway
• Penicillin and cephalosporin are β lactam
antibiotics. β lactam antibiotics are produced
by a few Ascomycota and several bacteria.
• The precursors of these antibiotics are amino
acids. Synthesis of active antibiotics is
directed by the inclusion in the growth
medium of different organic and fatty acids
resulting in different side chains on the
compound.

17. • A second group of antibiotics derived from the
amino acid pathway are the defensins.
Defensins are peptides that act against
bacteria. They are found in animals where
they function to protect organs such as the
gingiva where bacterial densities are very
high. The first defensin found in fungi has
been called plectasin. The role of plectasin in
its host Pseudoplectania nigrella is unknown.

18. • Toxins derived from amino acid synthesis
include psilocybin (Psilocybe) and Bufotenine
(Amanita).
• These compounds act on nerve impulses,
resulting in hallucinations. The result is
thought to be due to the similarities between
the compounds and serotonin

19. Combination of Pathways
• Ergot alkaloids are synthesised from several
pathways. Trypotophan from the shikimic acid
pathway is attached to an isoprenoid moiety
from the mevalonate pathway, and several
amino acids from primary metabolism are added
depending on the final product. Ergot alkaloids
are produced as a complex mixture of related
compounds from a branched pathway.
• The activity of the alkaloids is as varied as the
compounds. In essence, the compounds may
function as vasodilators, hormone regulators,
and feeding deterrents. They can be active in
mammals and insects.