Biosynthesis Pathways, Transport Mechanisms and Biotechnological Applications of Fungal Siderophores

Abstract

Iron (Fe) is the fourth most abundant element on earth and represents an essential nutrient for life. As a fundamental mineral element for cell growth and development, iron is available for uptake as ferric ions, which are usually oxidized into complex oxyhydroxide polymers, insoluble under aerobic conditions. In these conditions, the bioavailability of iron is dramatically reduced. As a result, microorganisms face problems of iron acquisition, especially under low concentrations of this element. However, some microbes have evolved mechanisms for obtaining ferric irons from the extracellular medium or environment by forming small molecules often regarded as siderophores. Siderophores are high affinity iron-binding molecules produced by a repertoire of proteins found in the cytoplasm of cyanobacteria, bacteria, fungi, and plants. Common groups of siderophores include hydroxamates, catecholates, carboxylates, and hydroximates. The hydroxamate siderophores are commonly synthesized by fungi. L-ornithine is a biosynthetic precursor of siderophores, which is synthesized from multimodular large enzyme complexes through non-ribosomal peptide synthetases (NRPSs), while siderophore-Fe chelators cell wall mannoproteins (FIT1, FIT2, and FIT3) help the retention of siderophores. S. cerevisiae, for example, can express these proteins in two genetically separate systems (reductive and nonreductive) in the plasma membrane. These proteins can convert Fe (III) into Fe (II) by a ferrous-specific metalloreductase enzyme complex and flavin reductases (FREs). However, regulation of the siderophore through Fur Box protein on the DNA promoter region and its activation or repression depend primarily on the Fe availability in the external medium. Siderophores are essential due to their wide range of applications in biotechnology, medicine, bioremediation of heavy metal polluted environments, biocontrol of plant pathogens, and plant growth enhancement.

Plant-Microbe Interaction in Sustainable Agriculture: The Factors That May Influence the Efficacy of PGPM Application

“…PGPR may produce siderophores, which are substances characterized by a low molecular weight involved in the chelation process of iron (Fe 3+ ) [182]. When iron is limited in the environment, microbic siderophores allow for the reduction of iron to the soluble form Fe 2+ , which is then released into the plant cell [65,69,183]. PGPR also enhance plant growth by producing very efficient extracellular siderophores, which allow the control of several plant disease by depriving the pathogens of iron nutrition [104].…”

Siderophores: a potential role as a diagnostic for invasive fungal disease

“…Fe 3þ -loaded siderophores are recognized by siderophore-specific transporters such as the members of the SIT family, which are expressed by fungal but not by mammalian cells [36,42]. Hence, uptake and intracellular enrichment of siderophores are limited to the pathogen.…”

“…Encouragingly, numerous genes of Aspergillus spp. associated with siderophore activity have been decoded [36,68].…”

“…As the host attempts to withhold free iron from the invasive cells, successful pathogens have developed strategies to undermine these defense attempts [35]. To increase the reservoir of available iron, a wide range of fungi reach beyond the immediate environment by secreting lowmolecular mass chelators with high iron affinity: the siderophores [33,34,36]. Using specific receptors and transporters, the fungus must then promote the uptake of the iron-loaded molecules, causing them to accumulate in the cells and thus in the focus of the infection [34,35,37].…”

A Siderophore Mimicking Gelation Component for Capturing and Self-Separation of Fe(III) from an Aqueous Solution of Mixture of Metal Ions

“…Many microorganisms, bacteria, and plants need Fe 3+ to perform their functions for survival. To overcome the limited availability and solubility in living systems, specialized proteins and small molecules work in tandem to synthesize “siderophores”, which are chelators specific for binding Fe 3+ . − From the environment, iron is acquired by living organisms or bacteria through the synthesis and secretion of siderophores . The selective transport systems can only do the active transport of the ferric complex after iron binding.…”