For centuries the smuts, with their systemic development from seed infection leading to their appearance at ear emergence (Figure 3.1), were a major prob-lem, particularly for cereal growers. Although hot water treatments developed in the 1920s served to partially alleviate seed infection, the development of the carboxamide (oxathiin) fungicides oxycarboxin and carboxin (Figure 3.6) in the mid 1960s reduced the cereal smuts to the status of minor pathogens. These remarkable compounds kill only basidiomycete fungi at low doses with little effect at such concentrations on plants, animals or indeed non-basidiomycete fungi. This extraordinary degree of specificity is due to the affinity of the com-pounds for part of the succinate dehydrogenase (SDH) complex of sensitive fungi. This enzyme is part of the tricarboxylic acid cycle in all organisms and its activity, and thus respiration, is blocked by carboxin and oxycarboxin at low dose, but only in rusts, smuts and related fungi. A slight difference in the amino acid structure of the SDH enzyme in sensitive fungi compared to SDH in other organisms allows binding of the fungicides at low dose, malfunction of this critically important enzyme and death of the pathogen.
The control of smut fungi by carboxin represents a major success story of the agrochemical industry. Carboxin is highly selective, applied at very low dose as a seed dressing (thus with virtually no risk of contamination of grain from the following harvest) and does not persist in the environment. Paradoxically, its low dose through use as a seed dressing and high efficacy against smut fungi has led to little profit to the manufacturing company when compared to returns from fungicides applied to foliage and stored products.
In the early 2000s, further developments in carboxamide fungicides have taken place (Figure 3.6). Silthiofam also has a narrow spectrum of activ-ity with the principal fungal target being the take-all root disease of cereals
Bupirimate
Fungicide Trade name Dose rate (g/ha)
Carboxin (1967) Vitavax (seed dressing) Silthiofam (2001) Latitude (seed dressing) Boscalid (2002) in Signum 270--470 (3)
Bupirimate (1976) Nimrod 175--350 (10) Figure 3.6 Carboxamides and bupirimate – systemic fungicides with a narrow
spectrum of activity.
that has proved very difficult to control by chemical means or the use of resis-tant cultivars. Silthiofam, like the carboxamides used for the control of smut fungi, appears to affect energy production in hyphae of the take-all fungus, but the mechanisms of selectivity are not clear. Boscalid, unlike other carboxam-ide compounds, has a wcarboxam-ide spectrum of activity and is used for the control of the grey mould Botrytis cinerea, powdery mildews and leaf spots in veg-etable crops. The basis of selectivity is not clear, but boscalid, like carboxin and oxycarboxin, inhibits SDH in sensitive fungal species.
The hydroxypyrimidine fungicides have a spectrum of activity as narrow as the carboximides, but their target is the powdery mildews. The only hydrox-ypyrimidine now used extensively is bupirimate (Figure 3.6). The selectivity of these fungicides appears to be due to inhibition of the enzyme adenosine
Cl
CH2Cl cyazofamid H3C
Dimethomorph (1994) 150 (8)
Prothiocarb (1984) Tattoo 1000 (5) Cymoxanil (1988) In Curzate 90 (no limit)
Cyazofamid (2001) 80 (8)
Zoxamide (2001) In Electis 150 Invader
Ranman
Dose rate (g/ha)
Figure 3.7 Phenylamide and other fungicides for oomycete pathogens.
deaminase in sensitive fungi. The precise mechanism of selectivity is not clear, but adenosine deaminase may not be present in plants and be of a slightly different structure in other fungi and non-target species.
The phenylamide fungicides metalaxyl and benalaxyl (Figure 3.7) were introduced in the late 1970s and offered the prospect of control of root-attacking species of the genera Pythium and Phytophthora, potato blight and the related
downy mildew fungi without recourse to soil drenching or repeated foliar application of protectant fungicides. Phenylamides are readily translocated in the xylem, and inhibit RNA polymerase activity in the ribosomes of sensitive fungi, probably by binding to a receptor in these organelles. Selectivity may be explained by differences in receptor morphology, such that the phenylamides only bind to receptors in the ribosomes of sensitive fungi.
Pesticide manufacturers see fungicides for potato blight and downy mildew control as a profitable area and several systemic compounds have been devel-oped in addition to the phenylamide group. Cymoxanil and dimethomorph (Figure 3.7) must have a different mode of action to phenylamides since these both inhibit phenylamide-resistant strains of oomycete fungi. Dimethomorph may interfere with cinnamic acid metabolism in sensitive fungi, but the mode of action of cymoxanil and the basis of selectivity of both these compounds is not known. Prothiocarb is slowly translocated in plants; its precise mode of action and mechanism of selectivity remains unclear but it may interfere with membrane function in sensitive fungal species.
Further developments in the early twenty-first century have included the introduction of zoxamide and cyazofamid, primarily for control of potato blight and downy mildew fungi. In sensitive fungi, zoxamide interferes with micro-tubule biosynthesis in a similar manner to the benzimidazoles (3.7.1). Inter-estingly, cyazofamid inhibits electron transport in sensitive fungi in a similar manner to the strobilurin fungicides (3.7.3), but at a different site in the respi-ratory chain. The basis of selectivity of cyazofamid may be due to binding of the fungicide to its active site only in oomycete fungi.
Strains of potato blight resistant to systemic fungicides developed for control of oomycete pathogens have arisen widely, most notably to the phenylamide compounds such as metalaxyl. To reduce the risk of resistance, most cura-tive and systemic fungicides for potato blight are marketed in mixtures with dithiocarbamate protectant compounds (3.3)