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FUNGAL METABOLISM AND FUNGAL PRODUCTS 137

prevented Fleming from producing penicillin con-
sistently, but which Florey and Chain solved by
rigorously controlling the fermentation conditions.
2 Recovery of penicillin from the culture filtrate and
treatment with penicillin acylase to produce 6-APA.
3 Chemical addition of specific acyl groups (R in
Fig. 7.16) to produce a range of “semisynthetic”
penicillins with different properties. For example,
oxacillin and closely related compounds are resis-
tant to some bacterial β-lactamases – the enzymes that
cleave the ring of penicillin G and thus inactivate
the antibiotic. Ampicillinhas significant activity
against some Gram-negative bacteria, whereas the nat-
ural penicillins act mainly against Gram-positives.
Penicillin V has enhanced resistance to degradation
by stomach acid, so it is one of the best penicillins
for oral administration, whereas penicillin G is sus-
ceptible to acid.

Despite these advances, all penicillins are susceptible
to breakdown by the plasmid-encoded β-lactamases of
some enteric bacteria, and penicillins cause allergic
reactions in some patients. These problems have been
approached by developing a structurally related group
of antibiotics, the cephalosporins, originally discovered
as products of a fungus called “Cephalosporium
acremonium”, but now produced commercially from
strains of bacteria (Streptomycesspp).

Mycotoxins

Mycotoxins are a diverse range of compounds from
different precursors and pathways. They typically
cause toxicity when humans or higher animals ingest
them over a relatively long period of time, from low
concentrations in improperly stored food or animal
feedstuffs. But we cannot exclude the possibility that
even brief exposures to these toxins are hazardous.

The problem in establishing this lies in the fact that

many years may elapse before the effects of exposure

become evident. A few representative examples of

mycotoxins are shown in Table 7.2. Edwards et al.(2002)

review the molecular methods for detecting these

compounds.

Many of the mycotoxin problems result from the

improper storage of food and feed products, and

therefore can be avoided (Chapter 8). But some

Fusariumspecies grow on the grains of standing cereal

crops in wet field conditions and can produce myco-

toxins before the grain is harvested. The Fusarium

toxins therefore pose particular problems. Several

examples are given in Table 7.2. Some toadstools also

contain deadly toxins, the classic examples being the

“death cap” Amanita phalloides, and the “destroying

angel” Amanita virosa. The toxicity of these is conferred

by the phallotoxinsand amatoxins, but these are

acutely toxic compounds and are not normally classed

as mycotoxins.

The ergot alkaloids and related toxins

The ergot fungus, Claviceps purpurea(Fig. 7.17) produces

sclerotia that develop in place of the grain in infected

cereals and grasses, then the sclerotia (termed ergots)

fall to the ground and overwinter near the soil surface.

In the following summer they produce minute fruit-

ing bodies, resembling drumsticks, which contain

many perithecia that release ascospores. The timing of

release of these ascospores coincides with the time

when the grass flowers open, so the fungus infects

the developing ovary and then develops into a new

sclerotium, to repeat the life cycle. The harvesting

and milling of ergot-contaminated cereals has caused

numerous deaths over the centuries. In one form of

the disease, termed convulsive ergotism, the nervous

system is affected and causes violent convulsions.

Table 7.2Some representative mycotoxins in foodstuffs.

Toxin

Aflatoxins
Ergot alkaloids
Fuminosins
Ochratoxin A
Patulin
Sporidesmin
Sterigmatocystin
Trichothecenes
Zearalenone

Effects

Nephrotoxic, hepatocarcinomas

Neurotoxic

Human esophageal cancer in Africa?

Nephrotoxic, kidney carcinoma

Contact edema, hemorrhage

Facial eczema of sheep, cattle

Hepatocarcinogen

Abortive, blistering, estrogenic

Vulvovaginitis

Foodstuff

Peanuts, oilseeds

Cereals, grasses

Maize

Grain crops

Apples

Grass

Grain, oilseeds

Cereals

Cereals

Representative fungi

Aspergillus flavus, A. parasiticus

Claviceps purpurea

Fusarium moniliforme

Some Aspergillus andPenicilliumspp.

Penicillium expansum, Aspergillus clavatus

Pithomyces chartarum

Aspergillus spp.

Fusarium spp.,Stachybotrys chartarum

Fusarium