175
et al. 2016). This chapter provides a brief discussion on fungal siderophores and
then describes the possible ways the fungal siderophores are and can be targeted to
overcome fungal diseases.
11.1.1 Siderophores
Iron is one of the essential elements for almost all living organisms, as it acts as a
catalyst in a wide variety of important metabolic processes (Yun et al. 2000). In an
iron-deficient condition, most of the plants, bacteria and fungi develop a unique iron
uptake and transport strategies for uptake and utilization of iron from their environment even when it exists in trace quantity. One such unique iron uptake strategy
includes the production and secretion of siderophores, small molecular weight compounds with high affinity for iron, especially ferric iron (Fe
3+
) (Ahmed and
Holmström 2014). Hence, siderophores act as ferric iron (Fe
3+
)–specific chelating
agents and thus help fungi to scavenge iron from the environment, transport it across
the cell membrane and thus make it available for the microbial cell.
Even though microbial siderophores are catecholates, and hydroxamates in
nature, fungal siderophores are mainly of hydroxamates and very few are carboxylates, polycarboxylate and phenolate (Eck et al. 1999; Hissen et al. 2005; Schrettl
et al. 2004; Tangen et al. 2007).
11.2 Iron Acquisition Mechanism
As discussed earlier, iron is required by almost all living organisms to perform normal cellular activities like distribution of oxygen, synthesis of genetic material and
ATP Production. At neutral pH and in the presence of oxygen, the chemical nature
of iron favours its oxidation from ferrous (Fe
2+
) to ferric (Fe
3+
). This rapid oxidation
leads to the formation of ferric oxyhydroxide (FeO(OH)) which is insoluble in
nature and this could not be taken up by the microbes (Heymann et al. 2002). Yet,
microbes require a minimum of 10
8
M concentration of iron for their optimal growth
and development but the bioavailability of iron lies between 10
−9
and 10
−18
M (Hu
et al. 2002). In order to overcome this iron shortage, microbes follow different iron
acquisition mechanisms. Although fungus has different iron acquisition mechanisms, the first four are quite common in nature (Ahmed and Holmström 2014;
Ismail et al. 1985). They are as follows:
1. Reductive iron acquisition
2. Siderophore biosynthesis
3. Utilization of siderophores by non-producers
4. Host molecule-specific iron acquisition
5. Acidification and mobilization
11 Siderophores in Antifungal Drug Discovery: A Computational Approach
et al. 2016). This chapter provides a brief discussion on fungal siderophores and
then describes the possible ways the fungal siderophores are and can be targeted to
overcome fungal diseases.
11.1.1 Siderophores
Iron is one of the essential elements for almost all living organisms, as it acts as a
catalyst in a wide variety of important metabolic processes (Yun et al. 2000). In an
iron-deficient condition, most of the plants, bacteria and fungi develop a unique iron
uptake and transport strategies for uptake and utilization of iron from their environment even when it exists in trace quantity. One such unique iron uptake strategy
includes the production and secretion of siderophores, small molecular weight compounds with high affinity for iron, especially ferric iron (Fe
3+
) (Ahmed and
Holmström 2014). Hence, siderophores act as ferric iron (Fe
3+
)–specific chelating
agents and thus help fungi to scavenge iron from the environment, transport it across
the cell membrane and thus make it available for the microbial cell.
Even though microbial siderophores are catecholates, and hydroxamates in
nature, fungal siderophores are mainly of hydroxamates and very few are carboxylates, polycarboxylate and phenolate (Eck et al. 1999; Hissen et al. 2005; Schrettl
et al. 2004; Tangen et al. 2007).
11.2 Iron Acquisition Mechanism
As discussed earlier, iron is required by almost all living organisms to perform normal cellular activities like distribution of oxygen, synthesis of genetic material and
ATP Production. At neutral pH and in the presence of oxygen, the chemical nature
of iron favours its oxidation from ferrous (Fe
2+
) to ferric (Fe
3+
). This rapid oxidation
leads to the formation of ferric oxyhydroxide (FeO(OH)) which is insoluble in
nature and this could not be taken up by the microbes (Heymann et al. 2002). Yet,
microbes require a minimum of 10
8
M concentration of iron for their optimal growth
and development but the bioavailability of iron lies between 10
−9
and 10
−18
M (Hu
et al. 2002). In order to overcome this iron shortage, microbes follow different iron
acquisition mechanisms. Although fungus has different iron acquisition mechanisms, the first four are quite common in nature (Ahmed and Holmström 2014;
Ismail et al. 1985). They are as follows:
1. Reductive iron acquisition
2. Siderophore biosynthesis
3. Utilization of siderophores by non-producers
4. Host molecule-specific iron acquisition
5. Acidification and mobilization
11 Siderophores in Antifungal Drug Discovery: A Computational Approach