Introduction to Fungi, Third Edition

304 PLECTOMYCETES
Fig11.14 Important metabolites produced byTrichocomaceae. (a) Penicillin G, an antibiotic against Gram-positive bacteria which is
synthesized from three amino acids.The cleavage point of penicillin acylases is indicated by an arrow. (b) Griseofulvin, an antifungal
antibiotic which is synthesized as a heptaketide, with three methyl groups (arrows) added subsequently by methylation. (c) The
polyketide aflatoxin B 1
. (d) Ochratoxin A.This is a pentaketide to which the amino acid phenylalanine is linked via a previously added
one-carbon group (arrow). (e) The derived tetraketide patulin.
partly to counter bacterial resistance and
partly to broaden the range of applications or
reduce allergic responses by patients. Current
production seems to be mainly semi-synthetic;
penicillin G is produced by P. chrysogenum,
followed by the removal of the side-chain to give
6-aminopenicillanic acid, which is then derivatized
chemically. There are tendencies to use
microbial enzymes (penicillin acylases) for the
removal of the side chain (see Fig. 11.14a) and for
subsequent synthetic steps (Arroyo et al., 2003;
Bruggink et al., 2003). Good general reviews of
the history of penicillin biotechnology have
been written by Rolinson (1998) and Demain and
Elander (1999). The biosynthesis of penicillins
and cephalosporins in fungi has been described
in detail by Martin et al. (1997).
Another important secondary metabolite of
the Trichocomaceae is griseofulvin (Fig. 11.14b),
which is used as a systemic antifungal drug,
especially against dermatophytes (see p. 293).
Griseofulvin was first detected in P. griseofulvum
(Oxford et al., 1939) and was then re-discovered in
P. janczewskii (see Brian, 1960). It is now known to
be produced by a wide range of Penicillium spp.
as well as Aspergillus versicolor and by the Hemiascomycete
Eremothecium coryli (Bérdy, 1986).
Commercial production is still achieved by
means of fungal fermentations.
11.4.4 Mycotoxins
Members of the genera Aspergillus and Penicillium
are notorious for their production of secondary
metabolites which are highly toxic against many
different organisms and are therefore collectively
called mycotoxins. Since these fungi are
often found as food contaminants, their mycotoxins
present a major health hazard and, consequently,
have been thoroughly investigated.
We summarize the major groups of substances
here, i.e. aflatoxins, ochratoxin A and patulin
(Figs. 11.14c e). These are derived at least in part
from the polyketide pathway in which acetylcoenzyme
A or malonyl-CoA units are fused
head-to-tail in a stepwise fashion. The principle