Abstract
Extremophiles are organisms able to thrive in extreme environmental conditions. Microorganisms with the ability to survive high doses of radiation are known as radioresistant or radiation-resistant extremophiles. Excessive or intense exposure to radiation (i.e., gamma rays, X-rays, and particularly UV radiation) can induce a variety of mutagenic and cytotoxic DNA lesions, which can lead to different forms of cancer. However, some populations of microorganisms thrive under different types of radiation due to defensive mechanisms provided by primary and secondary metabolic products, i.e., extremolytes and extremozymes. Extremolytes (including scytonemin, mycosporine-like amino acids, shinorine, porphyra-334, palythine, biopterin, and phlorotannin, among others) are able to absorb a wide spectrum of radiation while protecting the organism’s DNA from being damaged. The possible commercial applications of extremolytes include anticancer drugs, antioxidants, cell-cycle-blocking agents, and sunscreens, among others. This article aims to review the strategies by which microorganisms thrive in extreme radiation environments and discuss their potential uses in biotechnology and the therapeutic industry. The major challenges that lie ahead are also discussed.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Radiation is energy in the form of electromagnetic waves (i.e., gamma rays, X-rays, UV radiation, radio waves, etc.) that causes oxidative damage to vital biomolecules such as proteins, DNA, RNA, and enzymes. One of its most basic forms is the UV radiation (UVR) in sunlight, which has been known to cause changes to the molecular structure of DNA by forming dimers between the strands of DNA molecules. As a result, UVR has been linked to many harmful effects in humans including immune suppression, dermatitis, premature aging, and, in extreme cases, skin cancer (Agar et al. 2004). Radiation from various nuclear facilities (e.g., radionuclides) has also been linked to acute health effects in humans. Increased exposure can cause fatigue, weakness, fever, hair loss, dizziness, diarrhea, and, in extreme cases, leukemia and leucopenia. In addition, this type of radiation has been linked to poor fetal development, including smaller brain size, abnormal growth, and mental retardation (Ghirga 2010).
However, extremophiles—organisms including microbes, plants, and animals that are able to survive in extreme environmental conditions, such as hot springs, volcanic areas, extreme temperatures, high salt levels, high antibiotic concentrations, and radiation—have found ways to survive (Gabani et al. 2012b; Kumar et al. 2010; Mesbah and Wiegel 2008). The microorganisms that thrive under extreme radiation are referred to as radiation-resistant or radioresistant extremophiles. They have been found in wide environmental niches such as higher elevations (mountain ranges) and open fields where UVR levels are high. The continuous depletion of the ozone layer has greatly influenced the amount of UVR in Earth’s biosphere. In addition, the extensive use of radioactive elements and compounds for energy, in medicine, research, and industry has produced radioactive wastes in the environment (Pryakhin et al. 2012). Nuclear accidents such as the Fukushima Daiichi nuclear disaster in 2011 and the Chernobyl disaster in 1986 have also caused an increase in radionuclides and radioisotopes in the environment. Other forms of radiation encountered in the environment include gamma radiation and X-rays, which are known to be harmful to humans.
Despite the harmful effects of radiation on humans, different types of microorganisms have found their ways to survive under high levels of radiation (Fig. 1). The bacterium Deinococcus radiodurans is capable of withstanding the supra-lethal effects of ionizing radiation and UVR (>1,000 J/m2) (Yuan et al. 2009a, b). Endolithic cyanobacteria are reported to be able to protect themselves from the harmful effects of UVR (Rastogi et al. 2010). Several microorganisms, such as Rhodanobacter sp. and Desulfuromonas ferrireducens have been observed to survive in the presence of high levels of radionuclides (Green et al. 2012). The ability of radioresistant organisms to survive high levels of radiation has been linked to their efficient DNA repair mechanisms and ability to produce protective primary and secondary metabolic products (Singh and Gabani 2011). The radiation-responsive metabolites, pigments, and enzymes they produce can be induced or activated by modern biotechnological techniques to produce useful drugs, especially anticancer drugs, as well as antibiotics and agricultural products of commercial significance (Kumar et al. 2010). However, the advantages of radiation resistant extremolytes and extremozymes in the field of therapeutic and biotechnology have not been implicated. This article aims to discuss the strategies by which microorganisms thrive in radiation-rich environments and their potential uses in biotechnology and the therapeutic industry. The major challenges that lie ahead are also discussed.
Types of radiation
Electromagnetic radiation of various types, including UVR and gamma rays (GR) continuously bombards the surface of the Earth. Most, if not all, UVR comes from the sun as a type of electromagnetic radiation with a wavelength of 10–400 nm and energies ranging from 3 to 124 eV. The continuous depletion of the ozone layer has increased the amount of UVR that reaches the surface of the earth. Because the skin is the largest organ of the human body, it faces a wide variety of harmful environmental factors, including UVR. UVR penetrates the layers of the epidermis, including keratinocytes, and leads to production of reactive oxygen species (ROS), which cause single and double DNA strand breaks, inflammation, immunosuppression, gene mutations, and ultimately carcinogenesis. Other types of DNA damage associated with UVR include cyclobutane pyrimidine dimmers and pyrimidine-pyrimidone(6-4) photoproducts leading to CC–TT or C–T transitions (Besaratinia et al. 2005) (Fig. 1). Among the mutations, the induction of cyclobutane pyrimidine dimers is well known to cause the alteration in the p53 gene, disrupting the normal cell cycle and shifting it towards carcinogenesis (Klein et al. 2010).
Similar to UVR, GR is also a form of ionizing radiation, and as a result, is biologically harmful to vital molecules such as DNA. Unlike UVR, which is mostly produced by the sun, GR is produced mainly by nuclear decay from high-energy-state atomic nuclei. Naturally occurring high-energy radioisotopes (i.e., potassium-40, uranium, and thorium) emit gamma radiation during their decay. GR is also generated as part of nuclear fission reactions, nuclear fusion reactions, lightning strikes, and cosmic rays (Fig. 1). The most common radioisotopes currently used in nuclear reactions are cobalt-60 (60Co), plutonium-239 (239Pu), uranium-238 (238U), radon-222 (222Rn), radium-226 (226Ra), thallium-201 (201Tl), iridium-192 (192Ir), cesium-137 (137Cs), and strontium-90 (90Sr) (Kurnaz et al. 2007). Currently, the most common result of acute radiation exposure (i.e., gamma radiation and radioisotopes) is radiation sickness with nausea, vomiting, and headaches but increased exposure can lead to fatigue, weakness, hair loss, diarrhea, and low blood pressure (Ghirga 2010). Prolonged exposure to radioisotopes and radionuclides can lead to leukemia, leucopenia, and damage to the internal organs, mainly the kidneys (Ghirga 2010). Despite the harmful effects of radiation, many microorganisms have evolved molecular mechanisms to combat the deadly effects and survive in the presence of radioisotopes and radionuclides as discussed below.
Life under radiation
Outer space is one of the most harsh and hostile environments in existence, with high vacuum, temperature fluctuations, a full spectrum of extraterrestrial solar electromagnetic radiation, and cosmic ionizing radiation. Cryptoendolithic microbial communities and epilithic lichens have survived long term (1.5 years) on the outer surface of the International Space Station (Onofri et al. 2012). In another study, Anabaena cylindrica, Nostoc commune, and Chroococcidiopsis were exposed to extraterrestrial UV spectrum (>110 or 200 nm) for 548 days in low Earth orbit. It was found that cells of A. cylindrica and Chroococcidiopsis survived, but N. commune did not (Cockell et al. 2011). Table 1 lists several species of extremophiles isolated from various environments that have been shown to be resistant different types of radiation.
The genus Deinococcus is found to be radioresistant as vegetative cells to large doses of ionizing radiation isolated from deserts, oceans, lakes, and marine fish (Shashidhar and Bandekar 2009; Yuan et al. 2009a, b; Zhang et al. 2007c). It has been determined that specific proteins such as single-stranded DNA binding proteins and UVR-tolerant DNA repair enzymes present in D. radiodurans are extremely important for gamma radiation resistance. Surprisingly, a novel strain of D. reticulitermitis sp. nov. with a survival rate of 34 % at a dose of 100 J/m2 UVR has also been isolated from a termite gut—not an environment regularly exposed to UVR (Chen et al. 2012). Table 2 summarizes several other species of Deinococcus found to be resistant to various forms of radiation.
Elevated resistance to gamma and UV radiation has been seen in Hymenobacter xinjiangensis, isolated from the desert of Xinjiang, China. This strain was also observed to be pink-pigmented, which may have played a role in the protection from UVR and gamma radiation (Zhang et al. 2007b). In Rubrobacter radiotolerance, the 24,000-Da monomer protein superoxide dismutase has been linked to the stability and survivability of this organism in the presence of GR (Terato et al. 2011). In a different study, it was reported that UVB radiation resulted in a 31.2, 14.4, and 6.3 % decrease in the use of amino acids, amines, and carboxylic acids and an increase in consumption of carbohydrates and phenolic compounds by 42.3 and 11.6 %, respectively, indicating a reduction in protein synthesis as a metabolic strategy to enhance survival (Santos et al. 2012).
An increase in trichloroacetic-acid-precipitable radioactivity has been reported in the culture supernatant of Chroococcidiopsis strains after X-ray irradiation, indicating an upregulation of excision processes involved in DNA repair pathways (Billi et al. 2000). It was recently reported that exposure of Halobacterium salinarum to various types of ionizing radiation induced the expression of ROS-scavenging enzymes as well as non-enzymatic antioxidant processes (Robinson et al. 2011). It was hypothesized that the carotenoids might function to absorb the radiation, allowing the survival of the bacterial strains. Another Gram-positive bacterium, Kineococcus radiodurans sp. nov., isolated from a radioactive work area, showed resistance to 3.5 kGy of gamma radiation, carotenoids with absorption maxima at 444, 471, and 501 nm (Phillips et al. 2002).
Microbial molecular elements under radiation
The modulated molecular elements from radiation-resistant extremophiles may be useful for targeting radiation-prone disease types. It is of interest to understand the changes in the genomics, proteomics, and metabolic profiles (i.e., metabolomics) of radioresistant organisms grown under radiation to gain an understanding of how these organisms survive (Singh 2006; Singh et al. 2011). The induction of uvrA in D. radiodurans reveals UvrABC system protein A with functions including DNA repair and survival of the organism in UVR. Additional proteins with differential regulation identified include recA, recD, recF, recG, recO, mutS, mutL, ruvB, etc. (Singh and Gabani 2011). Our studies revealed that microorganisms, i.e., Cellulosimicrobium cellulans (UVP1) and Bacillus pumilus (UVP4), grown under radiation show differential expression of many yet to be identified proteins and metabolites (Gabani et al. 2012a). In the gamma-radiation-resistant Bacillus sp. HKG 112, two proteins, 38 kDa flagellin and 86.5 kDa S-layer protein, showed significant changes after radiation exposure (Gupta et al. 2011). Liedert et al. (2010) reported that in D. geothermalis, there were 34 abundant proteins that had no known function; these might relate to the extreme stress tolerance of the organism.
Several studies have focused on the potentially novel proteins in the nucleoids of radioresistant organisms. A comparative proteomics analysis of D. radiodurans and Deinococcus deserti revealed that the histone-like DNA-binding protein HU was the most abundant protein among the nucleoid-associated proteins (de Groot et al. 2005). D. radiodurans contains two LexA homologues, LexA1 and LexA2, which are hypothesized to be transcriptional regulators associated with DNA damage response. It was found that in a LexA2 disruptant strain, a pprA promoter was activated and a subsequent increase in the novel-radiation-inducible protein PprA noticed as reviewed in Singh and Gabani (2011). The presence of highly efficient DNA repair enzymes in D. radiodurans allows it to repair hundreds of double-stranded DNA breaks. Deletion of a novel polymerase, X family DNA polymerase, showed a decrease in the rate of repair of double-stranded DNA breaks and also an increase in sensitivity to GR (Leulliot et al. 2009). In addition, the increased expression levels of general stress protein DR1199 in D. radiodurans may be involved in the detoxification of the cell from ROS (Leulliot et al. 2009).
In addition to the identification of genes, proteins have been studied to determine their function in radiation resistance. In Amphibacillus sp. KSUCr3, a membrane-bound chromate reductase (for reduction of Cr(VI)) was found to be maximally active at 40 °C and a pH of 10.5 (Ibrahim et al. 2012). In Chlamydomonas sp. ICE-L isolated from Antarctic ice, the presence of UVB radiation increased the levels of Hsp70 protein approximately threefold (Liu et al. 2010). It was reported that in the presence of UVR, the expression of RadB and RadA in Sulfolobus tokodaii was increased. It was also reported that RadA and RadB preferred to bind to ssDNA and ssDNA-dependent ATPase (Sheng et al. 2008).
Dictyostelium discoideum, known as a DNA damage extremophile, is able to survive extremely high doses of radiation and DNA crosslinking agents due to the presence of the Fanconi anemia pathway (FA), translesion synthesis (TLS), and nucleotide excision repair. Zhang et al. (2009) revealed that disruption of Xpf nuclease in D. discoideum resulted in extreme hypersensitivity to crosslinks and radiation. It was also revealed that Xpf nuclease functioned with FA and TLS gene products (Zhang et al. 2009). Another study found that the protein Dclre1 was responsible for repair of double-strand breaks caused by radiation (Hsu et al. 2011). Muller-Taubenberger et al. (2011) reported that the presence of Dot1 contributed to UV radiation resistance in D. discoidium. Nath and Bharathi (2011) reviewed transcripts and the translational pattern of stress proteins in extremophiles.
Benefits of radiation-resistant extremophiles
The secondary metabolic reserves of extremophiles (i.e., extremolytes and extremozymes) are not involved in the direct survival, growth, development, and reproduction of the organism. However, the presence of these secondary metabolites does affect microbial survival when exposed to radiation. The unique features of extremolytes allow for far-reaching applications in biotechnology, ranging from bioremediation of nuclear waste products to the production of medically important drugs reviewed in Singh and Gabani (2011).
Therapeutic implications of radiation-resistant extremolytes
Progress has been made in searching for extremophiles that produce extremolytes with indications for anticancer drugs. To date, several UVR-protective compounds have been isolated from UVR-resistant extremophiles, including Mycosporine-like amino acids (MAAs), scytonemin, ectoine, bacterioruberin, sphaerophorin, pannarin, and melanin. Table 3 summarizes different microbial metabolic products that have been isolated from UVR-resistant extremophiles and their therapeutic implications.
MAAs are characterized by a cyclohexenone or cyclohexenimine core conjugated with the nitrogen moiety of an amino acid, and are synthesized by the shikimic acid pathway via 3-dehydroquinic acid and 4-deoxygadusol, a known strong antioxidant (Shick and Dunlap 2002). MAAs have been isolated from red algae, sea stars, corals, dinoflagellates, and cyanobacteria with UVB irradiation (Shick and Dunlap 2002). A novel mycosporine isolated from the lichenized ascomycete Collema cristatum showed protection against UVR-induced membrane destruction, pyrimidine dimer formation, and erythema in cultured human keratinocytes (Russo et al. 2008). Due to the ability of MAAs to absorb UVR, they present as compounds that can be added to UV sunscreens. It has been found that the sunscreen ability of MAAs is greatly enhanced when they are applied extracellularly, indicating their role in photoabsorption (de la Coba et al. 2009); they can be used in the cosmetic industry to enhance the protective effects.
An alternate physiological role for MAAs is as antioxidants. Some forms of MAAs (Table 3) have been known to scavenge ROS produced by UVR exposure. In other species of extremophiles that produce MAAs, the biosynthesis can also be induced by osmotic shocks. A formulation of MAAs (Porphyra-334 and Shinorine) has been shown to maintain the antioxidant defense system of the skin in the presence of UVR-induced skin damage in mice (de la Coba et al. 2009). The authors (de la Coba et al. 2009) also showed that the formulation prevented stratum corenum, malphigian, dermal, and hypodermal thickening. Various other MAAs that have been shown to have antioxidant as well as photoprotective roles include palythine, asterina, palythinol, and palythene (Llewellyn and Airs 2010). Gao and Garcia-Pichel (2011) broadly reviewed the biosynthesis and the biochemistry of MAAs. While the MAAs are promising, their direct therapeutic implications as drug candidates have yet to be studied.
In addition to MAAs, scytonemin, a yellow to brown and lipid-soluble compound from cyanobacteria, has also shown promise as a sunscreen. Scytonemin is a symmetrical indole-alkaloid consisting of fused heterocyclic units, connected via a carbon–carbon bond (Fig. 2). This complex ring structure and its conjugated double bonds make the compound particularly stable and allow for the absorption of UVR. Spectrophotometric analysis has revealed that the sheath of scytonemin is effective in shielding the cells from incoming UVR but not visible light. Mechanisms to induce the production of scytonemin need to be identified in order to explore its biotechnology implications. Several studies have revealed that temperature and photo-oxidative stresses alone do not increase the levels of scytonemin in cyanobacteria (Dillon et al. 2002; Fleming and Castenholz 2008). However, a combination of UVA irradiation and the previously mentioned stresses is effectively able to increase levels of scytonemin (Dillon et al. 2002) (Fig. 3). Desiccation along with lack of fixed nitrogen and UVA irradiation has been reported to trigger the production of scytonemin in culture medium (Fleming and Castenholz 2008).
Soule et al. (2009) studied the biosynthesis of scytonemin, governed by a set of 18 gene clusters (NpR1276 to NpR1259), in Nostoc punctiforme ATCC 29133. In the proposed model, the genes downstream of the open reading frame (ORF) NpR1273 (scyD) encoded enzymes in the aromatic amino acid pathways. Furthermore, UVA radiation was able to induce trp and typ genes leading to the production of tryptophan and p-hydroxyphenyl pyruvate monomers likely to be involved in the biosynthesis of scytonemin (Soule et al. 2009).
Scytonemin has also been investigated as an ATP-competitive inhibitor of polo-like kinases (PLKs). Because PLKs control many oncogenes, become the target in cancer research for many years. Stevenson et al. (2002) showed that scytonemin was able to inhibit PLK1 in flash plate screening assays and showed the ability to treat hyperproliferative disorder (Fig. 3). In another study, scytonemin-mediated inhibition of PLK1 was able to induce apoptosis in osteosarcoma and other cancer cell types, suggesting that scytonemin may provide a novel pharmacophore for the development of protein kinase inhibitors as antiproliferative and anti-inflammatory drugs (Duan et al. 2010).
Several other compounds that have shown potential as therapeutics are ectoine, bacterioruberin, sphaerophorin, and pannarin. Buenger and Driller (2004) showed that UVA-irradiated human keratinocytes were protected from damage when ectoine was applied. Ectoine has also been shown to prevent damage induced by bacterial lipopolysaccharide by elevating levels of Hsp70 protein (Buommino et al. 2005). Bacterioruberin isolated from Rubrobacter radiotolerans may have a potential use in human therapeutics to repair damaged DNA strands caused by ionizing radiation and prevent skin cancer (Asgarani et al. 2000). Sphaerophorin and pannarin, isolated from lichens, have been evaluated for their ability to repair DNA damage induced by hydroxyl radicals, nitric oxide, and superoxide anion (Russo et al. 2008).
Ectoine has been widely studied for its ability to protect skin against water loss, desiccation, and UV damage (Buenger and Driller 2004). It was found that ectoine was able to protect skin from damage caused by sodium dodecyl sulfate and water loss as well as having a prophylaxic effect against dry skin. It has been proposed that this mechanism underlies the ability of Ectoin to block second messenger systems, transcription factor AP-2, intracellular adhesion molecule-1 expression, and prevent mitochondrial DNA mutations (Fig. 3c). In addition, the effect of ectoine is especially pronounced within the Langerhans cells, which present antigens crossing the skin barrier and induce T cell immune response. (Buenger and Driller 2004). In another study, it was found that ectoine played a cytoprotective role when cells were exposed to bacterial lipopolysaccharides (Buommino et al. 2005).
Biotechnological implications of radiation-resistant extremolytes
In addition to the therapeutic implications, recent studies have also implicated many biotechnological applications of radiation-resistant extremolytes. The use of radiation-resistant extremophiles in the bioenergy sector has not been extensively studied. The current challenge is to find an efficient and inexpensive process for the degradation of complex carbohydrates to produce bioethanol. Gabani et al. (2012a) reportedly isolated two novel strains of C. cellulans UVP1 and B. pumilus UVP4 that were able to survive in the presence of 1.03 × 106 J/m2 and 1.71 × 105 J/m2UVC, respectively. Both C. cellulans and B. pumilus showed a tremendous ability to degrade cellulose under varying physical and chemical conditions (high temperature, high salt content, and acidic pH).
Radiation-resistant extremolytes have also been implicated for the bioremediation of nuclear waste. The enzyme c-type cytochrome in Shewanella putrefaciens and Geobacter sulfurreducens (Lloyd et al. 2003) has been found to reduce soluble uranium radioisotopes into insoluble species. In Desulfovibrio desulfuricans, it was observed that a Ni-Fe hydrogenase was able to reduce Tc (VIII) (Luca et al. 2001). Fujimoto and Morita (2006) isolated a novel strain of Halomonas sp. that was able to remove technetium from solution by making it insoluble. Kim et al. (2012) showed Geobacter sp. and Rhodoferax ferrireducens had the metabolic potential to reduce radioisotopes via enzymatic mechanisms similar to those discussed above.
Indirect enzymatic reduction of radionuclides has also been implicated as a way to bioremediate soil contaminated with nuclear waste. For this process, metal-reducing and sulfate-reducing microorganisms can be used to indirectly reduce soluble radionuclides. In this mechanism, the oxidation of organic compounds or hydrogen is coupled with the reduction of iron Fe(III) or sulfur S(IV) in the form of sulfate. This product can then be reduced further into multi-component insoluble species (van Hullebusch et al. 2005). For example, sulfate-reducing bacteria such as Micobacterium flavescens are capable of producing compounds such as organic acids, siderophores, and extracellular metabolites when grown in the presence of U, Th, Am, and Pu.
In addition to being reduced to their insoluble form, radionuclides can be adsorbed by radiation-resistant extremophiles. A brown marine algae Cystoseira indica showed effective adsorption of uranium radioisotope (Seyrig 2010). Other microorganisms showing effective adsorption of radionuclides include Citrobacter freudii and Firmicutes sp. Wu et al. (2006) developed a method to bioremediate high concentrations of uranium radioisotopes with the addition of ethanol.
Radioresistant organism D. radiodurans has been proven effective in bioremediation of heavy metals from acidic and neutral water (Misra et al. 2012). Misra et al. (2012) found that D. radiodurans was able to remove 70 % of 1 mM input uranium solution. In addition to heavy metals, D. radiodurans has been used for bioremediation of phthalate esters, which are widely used in cosmetics, perfumes, and plasticizers (Liao et al. 2010). This ability of D. radiodurans for bioremediation can be multiplied to include even more substrates with proper genetic engineering of the organism.
Many therapeutic and industrial applications of extremolytes and extremozymes have been patented; some from the past decade are summarized in Table 4. Verenium Corporation holds nine different patents for the development of thermostable enzymes via mutagenesis of thermophiles. This allows the corporation to manufacture enzymes that are stable and twice as efficient at high temperatures (>60 °C). Biotop AG uses a continuous fermentation method to produce Ectoin on a large scale for applications such as cosmetics and therapeutics. In a clinical trial conducted by Biotop AG, it was found that patients receiving eye drops and nasal sprays of ectoin, the symptoms of acute allergic rhinitis were significantly reduced.
Limitations and challenges in a 5-year view
The development of new-generation therapeutics, such as sunscreens and anti-cancer metabolites, with lack of allergenic potential in humans is promising (Siezen 2011). Because metabolites from extremophiles are naturally selected through evolution, they are considered to be environmentally friendly. The recent developments in “-omics”-based technologies (genomics, proteomics, and metabolomics) could assist in microbial biosynthesis of potential metabolites using genetically engineered microorganisms in bioreactors (Singh 2006; Singh et al. 2011). Several extremolytes and/ or manufacturing processes have been patented for use in pharmaceutical and cosmetic applications (Table 4). Many MAAs (i.e., Helioguard 365 and Helionori) from extremophiles are currently commercialized as sunscreen products for UVR protection due to their broad UVR absorption spectrum (de la Coba et al. 2007). In addition, scytonemin has potential to be the next “all in one” drug to prevent skin damage from UVR, cancer, and inflammation (de la Coba et al. 2009). However, because the biological activity of scytonemin is not well understood, further studies are required to understand its potential effects in humans. Lastly, melanin is widely used in the manufacturing of photo-protective sunscreens, but the production of melanin is becoming more and more expensive due to its complex molecular structure. Bacterial production of melanin promises an inexpensive way of obtaining melanin relatively easily (Liu and Simon 2003).
Current and future perspectives on extremophile metabolism, genetics, and physiology will likely yield new breakthroughs in biotechnological applications. In addition, future research in refinement of culture media, cell–cell communication, and high-throughput innovations can lead to novel insights into environments that were once thought to harbor no forms of life.
Despite current breakthroughs in the area of biotechnology, there are always limitations involved in producing effective extremolytes for human usage. One of the main limiting factors for the commercialization of extremozymes and extremolytes is the identification of the correct media to maximize production. The media need to have suitable nutrient, pH, and temperature levels (Copeland et al. 2012). Even slight variations in pH and temperature could greatly influence the metabolism of extremophiles. The amount of essential nutrients required also limits the product concentration; however, to overcome the nutrient limitation, fed-batch cultivation has been adapted widely and is currently used most often for cell culture processes (Copeland et al. 2012). In addition, product recovery remains one of the most limiting factors for commercialization of extremozymes and extremolytes.
Conclusions
The ecology of various radioresistant microorganisms and their potential in biotechnology are imperative in today’s modern technology. Studying the biology, genetics, and molecular mechanisms of extremophiles is essential in understanding the limits of life and may help us answer the question of whether life exists in extreme conditions on other planets. Here, we have described various radioresistant organisms and their habitats, which are unfriendly to most other forms of life. Knowledge of the evolution of extremophiles in extreme environments will increase our understanding of the evolutionary process and the genetic and molecular consequences of extreme environments. The biotechnological implications of radioresistant extremophiles are also of great importance. Radiation-resistant extremophiles provides limitless opportunities in human therapeutics, pharmaceuticals, biotechnology, and biodegradation of toxic and radioactive compounds. Because of the ability of extremophiles to survive in high radiation, the various metabolites and enzymes they produce can be manufactured and used for human therapeutics as well as bioremediation of radioactive compounds in nuclear waste fields. However, increased research efforts need to be made to fully investigate the potential of radiation-resistant extremophiles in therapeutic and biotechnological applications.
References
Agar NS, Halliday GM, Barnetson RS, Ananthaswamy HN, Wheeler M, Jones AM (2004) The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: a role for UVA in human skin carcinogenesis. Proc Natl Acad Sci U S A 101(14):4954–4959
Aguilera JA, Bischof KB, Karsten UK, Hanelt DH, Wiencke CW (2002) Seasonal variation in ecophysiological patterns in macroalgae from an Arctic fjord. II. Pigment accumulation and biochemical defence systems against high light stress. Mar Biol 140(6):1087–1095
Asgarani E, Terato H, Asagoshi K, Shahmohammadi HR, Ohyama Y, Saito T, Yamamoto O, Ide H (2000) Purification and characterization of a novel DNA repair enzyme from the extremely radioresistant bacterium Rubrobacter radiotolerans. J Radiat Res 41(1):19–34
Asker D, Awad TS, Beppu T, Ueda K (2008) Deinococcus misasensis and Deinococcus roseus, novel members of the genus Deinococcus, isolated from a radioactive site in Japan. Syst Appl Microbiol 31(1):43–49
Asker D, Awad TS, Beppu T, Ueda K (2009) Deinococcus aquiradiocola sp. nov., isolated from a radioactive site in Japan. Int J Syst Evol Microbiol 59(Pt 1):144–149
Asker D, Awad TS, McLandsborough L, Beppu T, Ueda K (2011) Deinococcus depolymerans sp. nov., a gamma- and UV-radiation-resistant bacterium, isolated from a naturally radioactive site. Int J Syst Evol Microbiol 61(Pt 6):1448–1453
Besaratinia A, Synold TW, Chen HH, Chang C, Xi B, Riggs AD, Pfeifer GP (2005) DNA lesions induced by UV A1 and B radiation in human cells: comparative analyses in the overall genome and in the p53 tumor suppressor gene. Proc Natl Acad Sci U S A 102(29):10058–10063
Billi D, Friedmann EI, Hofer KG, Caiola MG, Ocampo-Friedmann R (2000) Ionizing-radiation resistance in the desiccation-tolerant cyanobacterium Chroococcidiopsis. Appl Environ Microbiol 66(4):1489–1492
Buenger J, Driller H (2004) Ectoin: an effective natural substance to prevent UVA-induced premature photoaging. Skin Pharmacol Physiol 17(5):232–237
Buommino E, Schiraldi C, Baroni A, Paoletti I, Lamberti M, De Rosa M, Tufano MA (2005) Ectoine from halophilic microorganisms induces the expression of hsp70 and hsp70B′ in human keratinocytes modulating the proinflammatory response. Cell Stress Chaperones 10(3):197–203
Callegan RP, Nobre MF, McTernan PM, Battista JR, Navarro-Gonzalez R, McKay CP, da Costa MS, Rainey FA (2008) Description of four novel psychrophilic, ionizing radiation-sensitive Deinococcus species from alpine environments. Int J Syst Evol Microbiol 58(Pt 5):1252–1258
Chen W, Wang B, Hong H, Yang H, Liu SJ (2012) Deinococcus reticulitermitis sp. nov., isolated from a termite gut. Int J Syst Evol Microbiol 62(Pt 1):78–83
Cockell CS, Rettberg P, Rabbow E, Olsson-Francis K (2011) Exposure of phototrophs to 548 days in low Earth orbit: microbial selection pressures in outer space and on early earth. ISME J 5(10):1671–1682
Conde FR, Carignan MO, Churio MS, Carreto JI (2003) In vitro cis-trans photoisomerization of palythene and usujirene. Implications on the in vivo transformation of mycosporine-like amino acids. Photochem Photobiol 77(2):146–150
Copeland E, Choy N, Gabani P, Singh OV (2012) Biosynthesis of extremolytes: radiation resistance and biotechnological implications. In: Singh OV (ed) Extremophiles: sustainable resources and biotechnological implications. Wiley, New York
de Groot A, Chapon V, Servant P, Christen R, Saux MF, Sommer S, Heulin T (2005) Deinococcus deserti sp. nov., a gamma-radiation-tolerant bacterium isolated from the Sahara Desert. Int J Syst Evol Microbiol 55(Pt 6):2441–2446
de la Coba F, Jose AA, Felix LF (2007) Use of mycosporine-type amino acid Porphyra-334 as an antioxidant. International Patent Number WO/2007/026035
de la Coba F, Aguilera J, de Galvez MV, Alvarez M, Gallego E, Figueroa FL, Herrera E (2009) Prevention of the ultraviolet effects on clinical and histopathological changes, as well as the heat shock protein-70 expression in mouse skin by topical application of algal UV-absorbing compounds. J Dermatol Sci 55(3):161–169
Di Capua C, Bortolotti A, Farias ME, Cortez N (2011) UV-resistant Acinetobacter sp. isolates from Andean wetlands display high catalase activity. FEMS Microbiol Lett 317(2):181–189
Dillon JG, Tatsumi CM, Tandingan PG, Castenholz RW (2002) Effect of environmental factors on the synthesis of scytonemin, a UV-screening pigment, in a cyanobacterium (Chroococcidiopsis sp.). Arch Microbiol 177(4):322–331
Duan Z, Ji D, Weinstein EJ, Liu X, Susa M, Choy E, Yang C, Mankin H, Hornicek FJ (2010) Lentiviral shRNA screen of human kinases identifies PLK1 as a potential therapeutic target for osteosarcoma. Cancer Lett 293(2):220–229
Fleming ED, Castenholz RW (2008) Effects of nitrogen source on the synthesis of the UV-screening compound, scytonemin, in the cyanobacterium Nostoc punctiforme PCC 73102. FEMS Microbiol Ecol 63(3):301–308
Fujimoto K, Morita T (2006) Aerobic removal of technetium by a marine Halomonas strain. Appl Environ Microbiol 72(12):7922–7924
Gabani P, Copeland E, Chandel AK, Singh OV (2012a) Ultraviolet-radiation-resistant isolates revealed cellulose-degrading species of Cellulosimicrobium cellulans (UVP1) and Bacillus pumilus (UVP4). Biotechnol Appl Biochem 59(5):395–404
Gabani P, Prakash D, Singh OV (2012b) Emergence of antibiotic-resistant extremophiles (AREs). Extremophiles 16(5):697–713
Gao Q, Garcia-Pichel F (2011) Microbial ultraviolet sunscreens. Nat Rev Microbiol 9(11):791–802
Ghirga G (2010) Cancer in children residing near nuclear power plants: an open question. Ital J Pediatr 36:60
Green SJ, Prakash O, Jasrotia P, Overholt WA, Cardenas E, Hubbard D, Tiedje JM, Watson DB, Schadt CW, Brooks SC, Kostka JE (2012) Denitrifying bacteria from the genus Rhodanobacter dominate bacterial communities in the highly contaminated subsurface of a nuclear legacy waste site. Appl Environ Microbiol 78(4):1039–1047
Gupta AK, Pathak R, Singh B, Gautam H, Kumar R, Arora R (2011) Proteomic analysis of global changes in protein expression during exposure of gamma radiation in Bacillus sp. HKG 112 isolated from saline soil. J Microbiol Biotechnol 21(6):574–581
Hsu DW, Kiely R, Couto CA, Wang HY, Hudson JJ, Borer C, Pears CJ, Lakin ND (2011) DNA double-strand break repair pathway choice in Dictyostelium. J Cell Sci 124(Pt 10):1655–1663
Ibrahim AS, El-Tayeb MA, Elbadawi YB, Al-Salamah AA, Antranikian G (2012) Hexavalent chromate reduction by alkaliphilic Amphibacillus sp. KSUCr3 is mediated by copper-dependent membrane-associated Cr(VI) reductase. Extremophiles 16(4):659–668
Im WT, Jung HM, Ten LN, Kim MK, Bora N, Goodfellow M, Lim S, Jung J, Lee ST (2008) Deinococcus aquaticus sp. nov., isolated from fresh water, and Deinococcus caeni sp. nov., isolated from activated sludge. Int J Syst Evol Microbiol 58(Pt 10):2348–2353
Joux F, Jeffrey WH, Lebaron P, Mitchell DL (1999) Marine bacterial isolates display diverse responses to UV-B radiation. Appl Environ Microbiol 65(9):3820–3827
Kampfer P, Lodders N, Huber B, Falsen E, Busse HJ (2008) Deinococcus aquatilis sp. nov., isolated from water. Int J Syst Evol Microbiol 58(Pt 12):2803–2806
Kerney KR, Schuerger AC (2011) Survival of Bacillus subtilis endospores on ultraviolet-irradiated rover wheels and Mars regolith under simulated Martian conditions. Astrobiology 11(5):477–485
Kim SJ, Koh DC, Park SJ, Cha IT, Park JW, Na JH, Roh Y, Ko KS, Kim K, Rhee SK (2012) Molecular analysis of spatial variation of iron-reducing bacteria in riverine alluvial aquifers of the Mankyeong River. J Microbiol 50(2):207–217
Klein AM, Brash DE, Jones PH, Simons BD (2010) Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia. Proc Natl Acad Sci U S A 107(1):270–275
Kumar R, Patel DD, Bansal DD, Mishra S, Mohammed A, Arora R, Sharma A, Sharma RK (2010) Extremophiles: Sustainable resource of natural compound- Extremolytes. In: Singh OV, Harvey SP (eds) Sustainable biotechnology: sources of renewable energy. Springer, Berlin, pp 279–294
Kurnaz A, Kucukomeroglu B, Keser R, Okumusoglu NT, Korkmaz F, Karahan G, Cevik U (2007) Determination of radioactivity levels and hazards of soil and sediment samples in Firtina Valley (Rize, Turkey). Appl Radiat Isot 65(11):1281–1289
Leulliot N, Cladiere L, Lecointe F, Durand D, Hubscher U, van Tilbeurgh H (2009) The family X DNA polymerase from Deinococcus radiodurans adopts a non-standard extended conformation. J Biol Chem 284(18):11992–11999
Liao CS, Chen LC, Chen BS, Lin SH (2010) Bioremediation of endocrine disruptor di-n-butyl phthalate ester by Deinococcus radiodurans and Pseudomonas stutzeri. Chemosphere 78(3):342–346
Liedert C, Bernhardt J, Albrecht D, Voigt B, Hecker M, Salkinoja-Salonen M, Neubauer P (2010) Two-dimensional proteome reference map for the radiation-resistant bacterium Deinococcus geothermalis. Proteomics 10(3):555–563
Liu Y, Simon JD (2003) Isolation and biophysical studies of natural eumelanins: applications of imaging technologies and ultrafast spectroscopy. Pigment Cell Res 16(6):606–618
Liu S, Zhang P, Cong B, Liu C, Lin X, Shen J, Huang X (2010) Molecular cloning and expression analysis of a cytosolic Hsp70 gene from Antarctic ice algae Chlamydomonas sp. ICE-L. Extremophiles 14(3):329–337
Llewellyn CA, Airs RL (2010) Distribution and abundance of MAAs in 33 species of microalgae across 13 classes. Mar Drugs 8(4):1273–1291
Lloyd JR, Leang C, Myerson ALH, Coppi MV, Cuifo S, Methe B, Sandler SJ, Lovley DR (2003) Biochemical and genetic characterization of PpcA, a periplasmic c-type cytochrome in Geobacter sulfurreducens. Biochem J 369:153–161
Luca D, van der Gon AWD, Anita V, Ponjee MWG, Brongersma HH, Popa G (2001) Surface nitridation processes and non-linear behaviour of the reactive magnetron discharge with titanium target. Vacuum 61(2–4):163–167
Mao J, Tang Q, Zhang Z, Wang W, Wei D, Huang Y, Liu Z, Shi Y, Goodfellow M (2007) Streptomyces radiopugnans sp. nov., a radiation-resistant actinomycete isolated from radiation-polluted soil in China. Int J Syst Evol Microbiol 57(Pt 11):2578–2582
Mesbah NM, Wiegel J (2008) Life at extreme limits: the anaerobic halophilic alkalithermophiles. Ann N Y Acad Sci 1125:44–57
Misra CS, Appukuttan D, Kantamreddi VS, Rao AS, Apte SK (2012) Recombinant D. radiodurans cells for bioremediation of heavy metals from acidic/neutral aqueous wastes. Bioeng Bugs 3(1):44–48
Muller-Taubenberger A, Bonisch C, Furbringer M, Wittek F, Hake SB (2011) The histone methyltransferase Dot1 is required for DNA damage repair and proper development in Dictyostelium. Biochem Biophys Res Commun 404(4):1016–1022
Nath IVA, Bharathi PAL (2011) Diversity in transcripts and translational pattern of stress proteins in marine extremophiles. Extremophiles 15(2):129–153
Nicholson WL, Ricco AJ, Agasid E, Beasley C, Diaz-Aguado M, Ehrenfreund P, Friedericks C, Ghassemieh S, Henschke M, Hines JW, Kitts C, Luzzi E, Ly D, Mai N, Mancinelli R, McIntyre M, Minelli G, Neumann M, Parra M, Piccini M, Rasay RM, Ricks R, Santos O, Schooley A, Squires D, Timucin L, Yost B, Young A (2011) The O/OREOS mission: first science data from the Space Environment Survivability of Living Organisms (SESLO) payload. Astrobiology 11(10):951–958
Onofri S, de la Torre R, de Vera JP, Ott S, Zucconi L, Selbmann L, Scalzi G, Venkateswaran KJ, Rabbow E, Sanchez Inigo FJ, Horneck G (2012) Survival of rock-colonizing organisms after 1.5 years in outer space. Astrobiology 12(5):508–516
Phillips RW, Wiegel J, Berry CJ, Fliermans C, Peacock AD, White DC, Shimkets LJ (2002) Kineococcus radiotolerans sp. nov., a radiation-resistant, gram-positive bacterium. Int J Syst Evol Microbiol 52(Pt 3):933–938
Pryakhin EA, Tryapitsina GA, Deryabina LV, Atamanyuk NI, Stukalov PM, Ivanov IA, Kostyuchenko VA, Akleyev AV (2012) Status of ecosystems in radioactive waste reservoirs of the Mayak Production Association in 2009. Heal Phys 103(1):61–63
Rainey FA, Ferreira M, Nobre MF, Ray K, Bagaley D, Earl AM, Battista JR, Gomez-Silva B, McKay CP, da Costa MS (2007) Deinococcus peraridilitoris sp. nov., isolated from a coastal desert. Int J Syst Evol Microbiol 57(Pt 7):1408–1412
Rastogi RP, Richa SRP, Singh SP, Hader DP (2010) Photoprotective compounds from marine organisms. J Ind Microbiol Biotechnol 37(6):537–558
Robinson CK, Webb K, Kaur A, Jaruga P, Dizdaroglu M, Baliga NS, Place A, Diruggiero J (2011) A major role for nonenzymatic antioxidant processes in the radioresistance of Halobacterium salinarum. J Bacteriol 193(7):1653–1662
Romero-Martinez R, Wheeler M, Guerrero-Plata A, Rico G, Torres-Guerrero H (2000) Biosynthesis and functions of melanin in Sporothrix schenckii. Infect Immun 68(6):3696–3703
Russo A, Piovano M, Lombardo L, Garbarino J, Cardile V (2008) Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sci 83(13–14):468–474
Santos AL, Oliveira V, Baptista I, Henriques I, Gomes NC, Almeida A, Correia A, Cunha A (2012) Effects of UV-B radiation on the structural and physiological diversity of bacterioneuston and bacterioplankton. Appl Environ Microbiol 78(6):2066–2069
Seyrig G (2010) Uranium bioremediation: current knowledge and trends. Basic Biotechnol eJournal 6(1):3
Shashidhar R, Bandekar JR (2009) Deinococcus piscis sp nov., a radiation-resistant bacterium isolated from a marine fish. Int J Syst Evol Microbiol 59:2714–2717
Sheng D, Zhu S, Wei T, Ni J, Shen Y (2008) The in vitro activity of a Rad55 homologue from Sulfolobus tokodaii, a candidate mediator in RadA-catalyzed homologous recombination. Extremophiles 12(1):147–157
Shick JM, Dunlap WC (2002) Mycosporine-like amino acids and related Gadusols: biosynthesis, acumulation, and UV-protective functions in aquatic organisms. Ann Rev Physiol 64:223–262
Shukla M, Chaturvedi R, Tamhane D, Vyas P, Archana G, Apte S, Bandekar J, Desai A (2007) Multiple-stress tolerance of ionizing radiation-resistant bacterial isolates obtained from various habitats: correlation between stresses. Curr Microbiol 54(2):142–148
Siezen RJ (2011) Microbial sunscreens. Microb Biotechnol 4(1):1–7
Singh OV (2006) Proteomics and metabolomics: the molecular make-up of toxic aromatic pollutant bioremediation. Proteomics 6(20):5481–5492
Singh OV, Gabani P (2011) Extremophiles: radiation resistance microbial reserves and therapeutic implications. J Appl Microbiol 110:851–861
Singh OV, Nagaraj NS, Gabani P (2011) Systems biology: Integrating ‘-omics’ oriented approaches to determine foodborne microbial toxins. In: Sahu SC, Casciano DA (eds) Handbook of systems toxicology: from omics technology to nanotechnology. Wiley, New York, pp 469–488
Soule T, Garcia-Pichel F, Stout V (2009) Gene expression patterns associated with the biosynthesis of the sunscreen scytonemin in Nostoc punctiforme ATCC 29133 in response to UVA radiation. J Bacteriol 191(14):4639–4646
Srinivasan S, Kim MK, Lim S, Joe M, Lee M (2012a) Deinococcus daejeonensis sp. nov., isolated from sludge in a sewage disposal plant. Int J Syst Evol Microbiol 62(Pt 6):1265–1270
Srinivasan S, Lee JJ, Lim S, Joe M, Kim MK (2012b) Deinococcus humi sp. nov., isolated from soil. Int J Syst Evol Microbiol. doi:10.1099/ijs.0.037234-0
Stevenson CS, Capper EA, Roshak AK, Marquez B, Eichman C, Jackson JR, Mattern M, Gerwick WH, Jacobs RS, Marshall LA (2002) The identification and characterization of the marine natural product scytonemin as a novel antiproliferative pharmacophore. J Pharmacol Exp Ther 303(2):858–866
Terato H, Suzuki K, Nishioka N, Okamoto A, Shimazaki-Tokuyama Y, Inoue Y, Saito T (2011) Characterization and radio-resistant function of manganese superoxide dismutase of Rubrobacter radiotolerans. J Radiat Res 52(6):735–742
Vaishampayan PA, Rabbow E, Horneck G, Venkateswaran KJ (2012) Survival of Bacillus pumilus spores for a prolonged period of time in real space conditions. Astrobiology 12(5):487–497
van Hullebusch ED, Peerbolte A, Zandvoort MH, Lens PN (2005) Sorption of cobalt and nickel on anaerobic granular sludges: isotherms and sequential extraction. Chemosphere 58(4):493–505
Wang W, Mao J, Zhang Z, Tang Q, Xie Y, Zhu J, Zhang L, Liu Z, Shi Y, Goodfellow M (2010) Deinococcus wulumuqiensis sp. nov., and Deinococcus xibeiensis sp. nov., isolated from radiation-polluted soil. Int J Syst Evol Microbiol 60(Pt 9):2006–2010
Weon HY, Kim BY, Schumann P, Son JA, Jang J, Go SJ, Kwon SW (2007) Deinococcus cellulosilyticus sp. nov., isolated from air. Int J Syst Evol Microbiol 57(Pt 8):1685–1688
Wu WM, Carley J, Fienen M, Mehlhorn T, Lowe K, Nyman J, Luo J, Gentile ME, Rajan R, Wagner D, Hickey RF, Gu BH, Watson D, Cirpka OA, Kitanidis PK, Jardine PM, Criddle CS (2006) Pilot-scale in situ bioremediation of uranium in a highly contaminated aquifer. 1. Conditioning of a treatment zone. Environ Sci Technol 40(12):3978–3985
Yang Y, Itoh T, Yokobori S, Shimada H, Itahashi S, Satoh K, Ohba H, Narumi I, Yamagishi A (2010) Deinococcus aetherius sp. nov., isolated from the stratosphere. Int J Syst Evol Microbiol 60(Pt 4):776–779
Yoo SH, Weon HY, Kim SJ, Kim YS, Kim BY, Kwon SW (2010) Deinococcus aerolatus sp. nov. and Deinococcus aerophilus sp. nov., isolated from air samples. Int J Syst Evol Microbiol 60(Pt 5):1191–1195
Yuan M, Zhang W, Dai S, Wu J, Wang Y, Tao T, Chen M, Lin M (2009a) Deinococcus gobiensis sp. nov., an extremely radiation-resistant bacterium. Int J Syst Evol Microbiol 59(Pt 6):1513–1517
Yuan YV, Westcott ND, Hu C, Kitts DD (2009b) Mycosporine-like amino acid composition of the edible red alga, Palmaria palmata (dulse) harvested from the west and east coasts of Grand Manan Island, New Brunswick. Food Chem 112(2):321–328
Yuan YV, Westcott ND, Hu C, Kitts DD (2009c) Mycosporine-like amino acid composition of the edible red alga, Palmaria palmata (dulse) harvested from the west and east coasts of Grand Manan Island, New Brunswick. Food Chem 112(2):321–328
Zenoff VF, Heredia J, Ferrero M, Sineriz F, Farias ME (2006) Diverse UV-B resistance of culturable bacterial community from high-altitude wetland water. Curr Microbiol 52(5):359–362
Zhang L, Li L, Wu Q (2007a) Protective effects of mycosporine-like amino acids of Synechocystis sp. PCC 6803 and their partial characterization. J Photochem Photobiol B 86(3):240–245
Zhang Q, Liu C, Tang Y, Zhou G, Shen P, Fang C, Yokota A (2007b) Hymenobacter xinjiangensis sp. nov., a radiation-resistant bacterium isolated from the desert of Xinjiang, China. Int J Syst Evol Microbiol 57(Pt 8):1752–1756
Zhang YQ, Sun CH, Li WJ, Yu LY, Zhou JQ, Zhang YQ, Xu LH, Jiang CL (2007c) Deinococcus yunweiensis sp nov., a gamma- and UV-radiation-resistant bacterium from China. Int J Syst Evol Microbiol 57:370–375
Zhang XY, Langenick J, Traynor D, Babu MM, Kay RR, Patel KJ (2009) Xpf and not the Fanconi anaemia proteins or Rev3 accounts for the extreme resistance to cisplatin in Dictyostelium discoideum. PLoS Genet 5(9):e1000645
Zhang L, Qin BF, Wang Y, Fang CX (2011) Deinococcus soli sp. nov., a gamma- and UV-radiation-resistant bacterium from north-west China. Mikrobiologiia 80(6):818–825
Acknowledgment
The authors thank Institutional assistance to make this research possible.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gabani, P., Singh, O.V. Radiation-resistant extremophiles and their potential in biotechnology and therapeutics. Appl Microbiol Biotechnol 97, 993–1004 (2013). https://doi.org/10.1007/s00253-012-4642-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-012-4642-7