Introduction to Fungi, Third Edition

CONTROL OF POWDERY MILDEW DISEASES
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Fig13.16 One of several possible sterol biosynthesis pathways
in fungi. Most fungi have ergosterol as their major membrane
sterol, but in the Erysiphales it is ergosta-5,24(28)-dien-3b-ol
(Loeffler et al.,1992). Putative targets of various sterol
biosynthesis inhibitors are indicated as follows. (1) Allylamines,
e.g. terbinafine (against Candida albicans;seeFig.10.9).
(2) Triazoles (against fungi pathogenic to humans as well as
plants). A specific demethylation step is inhibited at C14.
(3) Morpholines, e.g. fenpropimorph (against plant-pathogenic
fungi).These compounds seem to inhibit two different steps
in sterol biosynthesis. Re-drawn and modified from
Kerkenaar (1995).
Morpholines (e.g. tridemorph; Fig. 13.15b) were
the first sterol biosynthesis inhibitors, acting by
inhibiting two sterol-modifying enzymes in fungi
(Fig. 13.16) whilst not affecting sterol biosynthesis
in plants (Kerkenaar, 1995; Uesugi, 1998). A more
recent fungicide, fenpropimorph, is derived
from tridemorph and has a similar mode of
action but is used against other fungi as well.
In contrast, the 2-aminopyrimidines (Fig. 13.15c)
act by inhibiting the incorporation of adenine
into nucleic acids, thereby halting DNA synthesis.
The effects are visible early, usually at the stage of
formation of the first haustorium (Holloman &
Schmidt, 1995).
Triazoles, which we have already encountered
as drugs in the treatment of Candida
infections (Fig. 10.9), are also extensively used
in agriculture because of their selective action in
sterol biosynthesis. There is a huge diversity of
structures (Kuck et al., 1995; Uesugi, 1998), but
they all seem to act as inhibitors of a cytochrome
P-450 involved in demethylating sterols at the C-
14 position (Fig. 13.16). These compounds are
therefore collectively called demethylation inhibitors
(DMIs). The target organism is unable to
produce a functional membrane. Triazoles are
active against a very wide range of fungal
pathogens and are systemic fungicides with
curative properties. One of the first important
examples against powdery mildews and other
biotrophic plant pathogens was triadimefon,
which is reduced in plants and fungi to its
more active alcohol (Fig. 13.15d). However,
resistance has arisen on numerous occasions,
and various resistance mechanisms have been