Siderophores
(from the Greek: iron carriers) are defined as
relatively low molecular weight, ferric ion specific
chelating agents synthesized by bacteria, actinomycetes,
fungi and certain algae growing under low ironic
stress. Chemically siderophores are iron binding
proteins with molecular weight ranging from 400
- 1500 Da. The role of these compounds is to scavenge
iron from the environment and to make the mineral,
which is almost always essential, available to
the microbial cell. Research in this field begun
about six decades ago, and interest in it accrued
with the realization that most aerobic and facultative
anaerobic microorganism synthesize atleast one
siderophore. Siderophores have been related to
virulence mechanisms in microorganism pathogenic
to both animals and plants. In addition, they
have applications in clinical, agricultural and
environmental fields. At present nearly 500 siderophores
are reported from selected microorganisms.
Importance
of iron in the environment and microbiology:
Iron is an important element
for most microorganisms owing to its importance
in biogeochemical reactions including respiration,
photosynthetic transport, nitrate synthesis,
nitrogen fixation and detoxification of oxygen
radicals. The aerobic atmosphere of the planet
has caused the surface iron to become converted
to oxyhydroxide polymers of very sparing solubility.
The concentration of free ferric ion at neutral
pH is dictated by the solubility product constant
of ferric hydroxide. In spite of the earth's
crust, dissolved iron concentrations are particularly
low.
A great variety of means
of acquisition, way of uptake and methods of
storage are used by microbes to ensure a supply
of the essential metal. Two methods commonly
used by microbes for acquisition of iron are
reduction and chelation. Solubilization of insoluble
iron polymers is the first step in iron assimilation.
Microorganisms growing under aerobic conditions
need iron for a variety of functions including
reduction of oxygen for the synthesis of ATP,
for formation of heme and for other essential
purposes. A level of atleast one micromolar
iron is needed for optimum growth.
Siderophores accumulate iron
and it transports the metal into the cell by
membrane receptor molecules, these molecules
are encoded by five genes in operon. These genes
used to mobilize, transport and uptake of this
essential element for the metabolism. The extreme
focus on the need for iron is reflected by its
requirement for the proper function of enzymes
that facilitates electron transport, oxygen
transport and other life sustaining processes.
Important
siderophore groups:
Important groups of siderophores
include hydroxamate siderophores, catecholate
(phenolates) siderophores and carboxylate siderophores.
Hydroxamate siderophores contain three secondary
hydroxamate groups, in which each hydroxamate
groups provides two oxygen molecules, which
form a bidentate ligand with iron. Hydroxamate
siderophores are produced by both bacteria and
fungi. Ferrichrome produced by the fungus Ustilago
sphaerogena, was the first siderophore to be
isolated and shown to be a growth factor for
other microbes.
Catecholate siderophores
are produced only by certain bacteria. Each
catecholate group provides two oxygen atoms
for chelation with iron so that a hexadentate
ochtahedral complex is formed as in the case
of hydraxamate siderophores. The best example
for catecholate siderophore is enterobactin
produced by E.coli. Carboxylates produced
by bacteria (certain Rhizobium and
Staphylococcus strains) and fungi belonging
exclusively to mucorales, coordinating iron
with carboxyl and hydroxyl groups.
Siderophore
producing microorganisms:
Siderophore synthesis, their
structure, properties and uses have been studied
for many terrestrial microorganisms. Wide range
of bacteria, fungi and countable number of actinomycetes
and algae are reported as produce different
kinds of siderophores
Bacteria:
Bacteria are common inhabitants
of metal contaminated sites, where they accumulate
and immobilize heavy metals. The cell walls
of gram positive bacteria have strong metal
binding properties. Some bacteria produce extra
cellular polysaccharide sheaths that bind metals.
In addition, metals such as manganese, nickel
and iron are absorbed through specific uptake
receptors. Under iron stress, bacteria produce
siderophores that bind ferric iron and transport
into an iron siderophore receptor. Bacteria
produce four types of siderophores: hydroxymate,
catecholate, salicylate and carboxylate. These
siderophores play an important role in the extra
cellular solubilization of iron from minerals
or organic substances. Some important siderophore
producing bacteria includes Escherichia
coli, Salmonella, Klebsiella pneumoniae, Vibrio
cholerae, Vibrio anguillarum, Aeromonas, Aerobacter
aerogens, Enterobacter, Yersinia and Mycobacterium
species.
Fungi:
Fungi are the important siderophore
producing microorganisms next to bacteria. Some
important siderophore producing fungi includes
Aspergillus nidulans, A. versicolor, Penicillium
chrysogenum, P. citrinum, Mucor, Rhizopus, Trametes
versicolor. Ustilago sphaerogina, Saccharomyces
cerivisiae, Rhodotorula minuta and Debaromyces
species.
Actinomycetes:
Actinomycetes are aerobic
gram positive filamentous bacteria with high
guanine + cytosine (G+C) content and form asexual
spores. Mostly they are saprophytic in nature
which prefer complex substrate for their growth
and able to tolerate certain metals at high
concentrations. Siderophore producing actinomycetes
includes Actinomadura madurae, Nocardia
asteroids, and Streptomyces griseus. Actinomycetes
produce both hydroxymate and salicylate types
of siderophores.
Algae:
Few algae also reported as
siderophore producers. Schizokinen, a dihydroxymate
type of siderophore, produced by Anabaena sp.,
reported to facilitate iron uptake. Anabaena
flos-aquae and Anabaena cylindrica
produce siderophores which accumulate copper.
Microbial
siderophores and marine ecosystem:
Surprisingly very little
is known about the nature of the siderophores
produced by marine microorganism. Structure
of anguibactin produced by a fish pathogen Vibrio
anguillarum and Bisucabarin produced
by a deep sea bacterium Alteromonas haloplanktis,
are known. Natural Dessferrioxamine G was produced
from marine Vibrio species. Strains of open
ocean bacteria from the genera Vibrio, Alteromonas,
Alkaligenes, Pseudomonas and Photobacterium
have been surveyed for their ability to produce
siderophores. Marine fungi includes Aspergillus
versicolor, Cunninghamella elegans, Rhizopus
species and Syncephalastrum racemosum
were found to be more potent siderophore producers.
In addition, marine phytoplankton Rhodomonas
ovalis were found to be a producer of siderophores.
In open ocean, the iron
content is low because of it's solubility nature
in sea water. When iron is scarce, marine bacteria
(and possibly some kinds of microalgae) make
siderophores. Most iron chelators are probably
siderophores or their break-down products. Siderophore
production and binding is part of specialized
biological machinery that helps these organisms
to harvest iron. This machinery includes not
only the siderophore-producing proteins, but
also cell-membranebound proteins that enable
ingestion of siderophore-complexed iron.
Siderophores effectively
increase the solubility of iron in sea water,
allowing ecosystems to support more microbes
by making more iron available for essential
biological processes. But chelated iron is available
only to organisms that can take it in.
Alison Butler, Jennifer Martinez
and their colleagues at UCSanta Barbara, in
collaboration with Margo Haygood's research
group at the Scripps Institution of Oceanography,
have isolated and characterized several siderophores
from marine microorganisms. These siderophores
are structurally quite different from known
terrestrial siderophores. Aquachelins from Halomonas
aquamarina DS40M3 and marinobactins from Marinobacter
sp. DS40M6 and DS40M8 both have an unusual water-insoluble
fatty acid part and a water-soluble peptide
part.
Applications
of microbial siderophores:
The importance of microbial
siderophores extends beyond their immediate
role in microbial physiology and their role
in biotechnology. Applications of microbial
siderophores for sustainability of humans, animals,
plants and environment is enormous.
Clinical
applications: As naturally occurring chelating
agents for iron, siderophores might be expected
to be some what less noxious for deferrization
of patients suffering from transfusion induced
siderosis. A siderophore from Streptomyces
pilosus, desfarrioxamine B, is marketed
as mesylate salt under the trade name Desferol
and is advocated for removal of excess iron
resulting from the suppurative therapy for Thalassemia.
The potency of common antibiotics has been elevated
by binding in to the iron binding functional
groups of siderophores.
Siderophore from Klebsiella
pneumoniae has been used as an antimalarial
agent. Sideromycin is an iron chelating antibiotic
produced by Streptomyces species showed
good antimicrobial activity.
Agricultural
interest:
Fluorescent Pseudomonads
form a line of siderophores comprised of a quinoline
moiety, responsible for the fluorescence and
a peptide chain of variable length bearing hydroxamic
acid and á- hydroxyl acid functions. Capacity
to form these Pseudobactin/ pyoverdine type
siderophores has been associated with improved
plant growth either through a direct effect
on the plant through control of noxious, organisms
in the soil. Nitrogenase can said to be an iron-intensive
enzyme complex and the symbiotic variety, as
found in
Rhizobium spp, may require
an intact siderophore system for expression
of this exclusively prokaryotic catalyst upon
which all life depends.
Environmental applications:
Siderophores have potential
ability to resolve various environmental problems
like heavy metal accumulation, rust removal,
biofouling, dye degradation, sewage treatment
and bioleaching, etc
Siderophores
in rust removal:
Rust consists predominantly
of Fe2O3 molecules
with trivalent iron ions. Traditional chemical
rust removal is based on two principles:
rust needs to be converted and then pickled.
Traditional, inorganic rust converters consist
predominantly of mineral acids, fat dissolvers
and corrosion inhibitors. These substances
react with the rust and form iron phosphate.
The use of natural acids such as malic or
citric acid has also proved successful.
However, the use of natural products requires
a lot of time (several hours to a whole
day) before satisfactory results can be
obtained.
Bacteria, fungi and plants
are using biological chelating compounds
in order to efficiently bind iron ions.
So rust layers can be abated in a natural
and gentle way. Biologists, mineralogists
and biotechnology engineers have been investigating
the process of biological rust removal for
many years.
Conclusion:
Iron is an important
element for all living cells. It is difficult
to take up iron into cells due to its poor
solubility. For the iron supply of living
cells, some microorganisms include bacteria,
fungi, actinomycetes and algae produce an
iron chelator, siderophore, outside the
cells and the siderophore is chelated with
ferric iron. There is an enormous scope
for the application of microbial siderophores
for the sustainability of humans, animals
and plants. Currently the applications of
siderophores in clinical, agricultural and
environmental sector are reported in some
extent. But the siderophore research is
not at all initiated in most of the microbiology
research laboratories. So, there is a need
to discover siderophores from normal and
also extremophiles in the ecosystems like
deep sea, desert and forest to exploit their
applications for welfare of all living beings
as well as for environment. Management Development
of bioprocess technology is also needed
for the industrial production of microbial
siderophores, since it has multisector applications.
| Organisms |
Siderophores |
Bacteria
Escherichia coli
Aeromonas hydrophila
Pseudomonas aeruginosa
Aerobacter aerogenes
Salmonella
Klebsiella sp.
Vibrio cholerae
Acinetobacter calcoacaticus
Mycobacterium tuberculosis
Yersinia pestis
Staphylococcus aureus
Fungi
Ustilago sphaerogina
Ustilago maydis
Aspergillus nidulans
Penicillium
Debaromyces
Rhodotoulaminuta
Actinomycetes
Actinomadura madurae
Nocardia sp.
Nocardia asteroides
Streptomyces griseus
|
Enterobactin
Amonabsactin
Pyoverdin and pyochelin
Aerobacin
Aerobactin
Aerobactin
Vibriobactin
Acinetobactin
Mycobactin
Yersniabactin
Aureochelin
Ferrichrome
Ferriaxamine B
Hydroxymate type
Hydroxymate type
Hydroxymate type
Hydroxymate type
Madurastatin
Nocobactin
Asterobactin
Desferrioxamine B
|
About the authors:
Dr. R. Balagurunathan,
Ph.D. is a Senior Lecturer and Head, Department
of Microbiology, Sri Sankara Arts & Science
College, Kanchipuram. He has obtained his
Ph.D from Centre of Advanced Study in Marine
Biology, Annamalai University, Parangipettai,
India and subsequently worked as Post Doctoral
Research Fellow at Malaysia and China. He
has successfully completed two research
projects and recently received a research
grant from DST, New Delhi for the discovery
of Antituberculosis Drugs from Actinomycetes.
He has 20 publications which includes, research
and review papers and chapters in book.
He has been working with high value metabolites
from extremophilic Actinomycetes.
M. Radhakrishnan, M.Sc.,
M.Phil., is a Lecturer in Microbiology
Department of Sri Sankara Arts and Science
College, Kanchipuram. He has several publications
which include research and review papers
and a chapters in book. His field of interest
is Actinomycetology - Actinomycetes Biology
and Technology.
| ENVIS
CENTRE Newsletter Vol.5, July 2007 |
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