Actinobacteria From Desert: Diversity and Biotechnological Applications

Deserts, as an unexplored extreme ecosystem, are known to harbor diverse actinobacteria with biotechnological potential. Both multidrug-resistant (MDR) pathogens and environmental issues have sharply raised the emerging demand for functional actinobacteria. From 2000 to 2021, 129 new species have been continuously reported from 35 deserts worldwide. The two largest numbers are of the members of the genera Streptomyces and Geodermatophilus, followed by other functional extremophilic strains such as alkaliphiles, halotolerant species, thermophiles, and psychrotolerant species. Improved isolation strategies for the recovery of culturable and unculturable desert actinobacteria are crucial for the exploration of their diversity and offer a better understanding of their survival mechanisms under extreme environmental stresses. The main bioprospecting processes involve isolation of target actinobacteria on selective media and incubation and selection of representatives from isolation plates for further investigations. Bioactive compounds obtained from desert actinobacteria are being continuously explored for their biotechnological potential, especially in medicine. To date, there are more than 50 novel compounds discovered from these gifted actinobacteria with potential antimicrobial activities, including anti-MDR pathogens and anti-inflammatory, antivirus, antifungal, antiallergic, antibacterial, antitumor, and cytotoxic activities. A range of plant growth-promoting abilities of the desert actinobacteria inspired great interest in their agricultural potential. In addition, several degradative, oxidative, and other functional enzymes from desert strains can be applied in the industry and the environment. This review aims to provide a comprehensive overview of desert environments as a remarkable source of diverse actinobacteria while such rich diversity offers an underexplored resource for biotechnological exploitations.


INTRODUCTION
A serious global health problem caused by pathogenic microorganisms is threatening human lives and welfare at an alarming speed. Due to abusive uses of antibiotics and antimicrobial prescriptions, the effectiveness of drugs and vaccines has been sharply decreased. Worse yet, the reduced interest from large pharmaceutical companies has further compromised the drug development process. To date, growing resistant infections have seriously jeopardized several of the United Nations (UN) Sustainable Development Goals (SDGs) related to the economy, global health, food production, and environment (Medina et al., 2020). Infectious diseases, such as malaria, HIV/AIDS, tuberculosis, and other communicable diseases, continue to pose risks to global health. In 2018, more than half a million new cases were caused by multidrugresistant (MDR) pathogenic infections, which remained the top deadly global disease during the past decade (World Health Organization, 2020). The large-scale use of antibiotics as growth promoters in agriculture also contributed to this crisis. As a result, more than 700,000 antimicrobial resistance-related deaths are predicted to happen annually worldwide in 2050, which could further reduce the global economy by $100 trillion as estimated by UN agencies (Medina et al., 2020). In particular, the pharmaceutical industry was unable to deliver effective drugs during the severe acute respiratory syndrome (SARS) epidemic between 2002 and 2003, causing a fatality rate of 11% (Chan-Yeung and Rui-Heng, 2003). Even today, 17 years later, there is still no anti-SARS drug available to cure the disease due to the slow progress in the development of post-epidemic drugs. Therefore, novel bioactive compounds to combat the threat of MDR pathogens and emerging diseases are urgently needed (Choudhary et al., 2016). Microbial natural products are considered as one of the important sources of bioactive compounds. Natural products are secondary metabolites (SMs) synthesized by bacteria and fungi and are not required for the growth, development, and reproduction of the producing organisms. In their native environments, these SMs may function as signaling molecules (Traxler and Kolter, 2015). SMs are attractive for drug discovery programs, in general, owing to their properties such as biochemical specificity, metabolic selectivity, structural diversity, and the potential to pass through eukaryotic outer membranes to block the production of cellular macromolecules and target enzymes (Baltz, 2008). To date, over 23,000 microbial natural products have been identified since the discovery of penicillin (Katz and Baltz, 2016).
Microorganisms isolated from extreme habitats are considered a significant reservoir for the search and discovery of new drugs. The most recent review revealed that 186 novel compounds were produced by 129 microbes (actinobacteria, cyanobacteria, fungi, and other bacteria) isolated from extreme habitats between 2010 and 2018 (Sayed et al., 2020). Cyanobacteria are known to generate antimicrobial (Micallef et al., 2015), antiprotozoal, and anti-inflammatory compounds (Vijayakumar and Menakha, 2015). Other bacteria reported to potentially synthesize bioactive metabolites are Thermus filiformis, which produced four antioxidant carotenoids, namely, all-trans-zeaxanthin, thermobiszeaxanthins, thermozeaxanthins, and zeaxanthin monoglucoside (Mandelli et al., 2012). Actinobacteria are shown to be the most frequent producer of specialized metabolites as compared to cyanobacteria and other bacteria (Sayed et al., 2020). The exploration of actinobacteria holds great promise in terms of diverse chemical libraries including antimicrobial compounds (erythromycin, gentamicin, vancomycin, daptomycin, and rifamycin), anticancer compounds (bleomycin, actinomycin D, and mitomycin), immunosuppressive compounds (rapamycin and tacrolimus), antiparasitic compounds (avermectins and spinosyns), and herbicidal compounds (bialaphos and glufosinate) and hence continued to drive innovative biotechnology (Krug and Müller, 2014;Katz and Baltz, 2016;Genilloud, 2017;Jose et al., 2021). Thus, actinobacteria are expected to play a significant role in biotechnological applications including in medical and agricultural sectors.
The genome sizes of actinobacteria ranged from 1 to 12 Mb with potent biosynthetic gene clusters (BGCs) encoded by biologically active compounds (Větrovský and Baldrian, 2013). The term "gifted actinobacteria" is first coined by Richard H. Baltz for actinobacteria with a large genome size, coding for more SM production than other taxa (Baltz, 2017). Quantitative analyses of microbial genomes performed by antiSMASH 3.0 revealed that these gifted actinobacteria harbored 20 to 50 SM gene clusters, allocating 0.8-3.0 Mb of the entire genome to SM production (Baltz, 2017(Baltz, , 2018. For example, gifted strains of Amycolatopsis, Micromonospora, and Streptomyces have moderate (about 5.0-7.9 Mb) or large (over 8 Mb) genomes, harboring 19-20 and >30 BGCs, respectively (Baltz, 2017(Baltz, , 2018(Baltz, , 2019Nouioui et al., 2019). Whole-genome analysis of these gifted genera usually revealed 20-50 BGCs encoding for both known and/or predicted specialized metabolites, which provides strong evidence that actinobacteria are promising producers of diverse novel compounds with various bioactivities (Bentley et al., 2002;Tang et al., 2016). For example, Streptomyces coelicolor A3(2) harbors more than 20 BGCs that encode for specialized metabolites such as blue-colored actinorhodin and red-pigment undecylprodigiosin (Bednarz et al., 2021). Similarly, the genome of Streptomyces sp. VN1 has shown diverse known and/or novel metabolites encoded by 34 gene clusters, involving a furan-type anticancer agent (Nguyen et al., 2020).
These genome sequence data also allowed the observation of genomic heterogeneity, which provides great insights into the ability of actinobacteria to synthesize diverse specialized metabolites (Jose et al., 2021). Generally, the genome size may correlate with a more complicated environment, implying that the genome encodes significant metabolic and stress-tolerant properties (Baltz, 2018). For example, Jiangella gansuensis YIM 002 T isolated from Gansu Desert has a complete genome sequence that identified 45 biosynthetic clusters, suggesting it has high capacity to produce SMs. Compatible solutes, ion transporters, nitrite reductase, and nitrogen fixation proteins were also detected . In addition, J. gansuensis YIM 002 T has a smaller genome (5.59 Mb) compared to other Jiangella species (more than 7 Mb), yet it contains 2,504 functional proteins, implying that it may have discarded many genes for adaptation in the harsh desert environments through its evolution . To defend against desert environmental stresses, superfluous and non-essential genes were discarded to improve survival efficiency, resulting in desert strains with higher metabolic capabilities compared with unevolved strains (Burke and Moran, 2011). Genome rearrangements were promoted by mobile DNA, which recombines inactive genes into functional genes, whereas inactivated genes were removed through deletion (Burke and Moran, 2011). This genomic evolution suggested that the reduction in genomic size of desert strains facilitated longterm adaptive evolution.

DESERT: AN UNEXPLORED RESERVOIR FOR NOVEL ACTINOBACTERIA
An increasing number of novel actinobacterial taxa continued to be reported from natural habitats, especially extreme biomes under harsh environmental conditions. These extreme habitats represent a potentially rich resource for novel compounds with biological properties. Particularly, the desert is the largest continental ecosystem on earth with approximately 30% of the total land area while 7% of it is a hyper-arid region with water constraints (Neilson et al., 2012). Desert ecosystems have attracted the increasing interest of microbiologists in the quest for novel bioactive compounds since they are considered an unexplored home of new extremophiles with high tolerance to extreme conditions. Desert environmental conditions are characterized by extremely high or low temperatures, lack of nutrients, very low organic carbon sources, high levels of oxidants and UV radiation or pH or salinity, high concentrations of metals, and other abiotic stresses (Horikoshi et al., 2010;Köberl et al., 2011;Bull et al., 2016;Idris et al., 2017a). The most explored desert soil sample has over 92% new actinobacterial species isolated. However, it is worth to note that the remaining 8% of novel species were found from desert plants, rhizosphere soil, and rock surfaces, respectively. Hence, such extreme conditions in the desert are considered as a selective pressure that shapes diverse actinobacterial communities.

Deserts in East Asia
Most deserts (31%) are distributed in China, East Asia (Figure 1 and Supplementary Table 1 (14). Despite being the largest desert in China, the Taklamakan Desert is the warmest and driest desert in the country, with an annual temperature of around 39 • C (Rittner et al., 2016). Additionally, as the second-largest non-polar and sand-shifting desert in the world, the Taklamakan Desert also experiences an extremely cold temperature (−32 • C) in winter and an extremely low average annual rainfall ranging from 10 to 38 mm (Rittner et al., 2016). Such severe environmental circumstances have attracted the attention of researchers for exploration of novel actinobacteria with exceptional tolerance in desert environments.

Deserts in Central and South Asia
Central Asia and South Asia are home to seven deserts, namely, Karakum Desert in Turkmenistan, Central Asia; Cholistan Desert in Pakistan; Kunjam Pass and Lahaul-Spiti Valley, two cold deserts in the Indian Himalayas; the saline desert of Kutch in India; Thal Desert in Pakistan; and Thar Desert in India (Supplementary Table 1). The Karakum Desert, in particular, was the isolation source of the most diverse (six genera) and numerous (11 new species) novel actinobacteria in Central and South Asia. It is one of the largest deserts in the world and the hottest desert in Central Asia (Ghassemi and Garzanti, 2019). In comparison to other deserts, the Karakum Desert is inhabited with animals and plants, mainly ephemeral plants, trees, and insects. Ninety-five percent of the area is more or less covered with vegetation, and the remaining 5% is sand dunes (Ghassemi and Garzanti, 2019). The annual average rainfall of Karakum Desert ranges from 70 to 150 mm. Its dry conditions are due to the fact that the coldest temperature of sand reaches −5 • C, while the hottest temperature climbs from 55 to 88 • C (Ghassemi and Garzanti, 2019). This dry but lively desert led many researchers to devise innovative projects that may benefit agriculture.

Deserts in the Middle East, North Africa, and South America
There are 12 deserts located in the Middle East, North Africa, and South America: Anatolia Desert in Turkey, Saudi Arabia arid area, Beni Suef Governorate Desert, Eastern Desert and saline-alkaline desert in Egypt, Béni Abbès Desert, Béni Isguen Desert and Sahara Desert of Algeria, Sahara Desert in Libya, arid-saline sediment, and Sahara Desert in Tunisia (Supplementary Table 1). The Atacama Desert in Chile, being the primary source of new actinobacterial species, accounts for around 20% of all new species (23) and half of all novel compounds (25) in the past two decades. The Atacama Desert is a hyper-arid or an extremely hyper-arid area according to the ratio of mean annual rainfall to mean annual evaporation of less than 0.05 or even below 0.002 (Bull et al., 2016). Being the driest desert in the world, the Atacama Desert has high temperatures during the day that can easily reach over 40-50 • C. The soil sample in the desert is very similar to the sample from Mars, with extremely low vegetation and organic carbon (about 2-50 µg of carbon per gram of soil) and high levels of UV radiation (Bull et al., 2016). Microbiologists are interested in the Atacama Desert as despite its harsh conditions, it harbors abundant and diverse actinobacteria with biotechnological potentials.

Deserts in Other Regions
Other new actinobacteria were discovered from the Antarctic Desert (South Pole), arid Australian soils (Oceania), Baja California Desert in Mexico (North America), Namib Desert in Namibia (South Africa), and Sahara Desert in Chad (Central Africa) (Supplementary Table 1). The highest number of new species was recorded from the Sahara Desert in Chad (6) and arid Australian soils (5). The Sahara Desert is the world's biggest hot desert, with extremely poor primary productivity, although it does sustain certain organisms that can adapt to arid environments, such as ephemerals (Schuster et al., 2006). The yearly precipitation in the Sahara Desert ranges from 0 to 7.62 cm, with some regions going for years without rain. The daily summer temperature of the Sahara Desert frequently exceeds 38 • C during the day but drops to near freezing at night. Arid Australian soils are characterized mainly by mineral or skeletal soils almost without any organic matter (Morton et al., 2011). The hot and dry weather is typical for the Australian arid lands with low annual precipitation (380-635 mm), frequent heatwaves, and high levels of solar radiation.
The two most dominant actinobacteria recovered from deserts are Streptomyces and Geodermatophilus. Streptomyces, the largest genus of actinobacteria, has the greatest number (16) of validly described desert actinobacterial species. To survive in desert environments, members of the genus Streptomyces have evolved a variety of tolerance mechanisms and bioactive compound potential. Currently, all reported bioactive compounds were derived from desert streptomycetes (Bérdy, 2005). For example, Streptomyces aburaviensis (Thumar et al., 2010), Streptomyces fukangensis (Zhang et al., 2013), and Streptomyces sannurensis (Hozzein et al., 2011) are alkaliphilic actinomycetes, with optimum growth at pH 9 to 11.5. S. aburaviensis (Thumar et al., 2010) and Streptomyces desertarenae (Li et al., 2019c) are halotolerant species that can adapt to living in high-saline environments (7-15% w/v NaCl), while Streptomyces asenjonii (Abdelkader et al., 2018) and Streptomyces leeuwenhoekii (Rateb et al., 2011a) were gifted for the synthesis of bioactive compounds with novel chemical structures. It should be noted that the majority of streptomycetes (7) was discovered from the Atacama Desert, including Streptomyces altiplanensis (Cortés-Albayay et al., 2019), Streptomyces atacamensis (Santhanam et al., 2012b), Streptomyces deserti (Santhanam et al., 2012a), and Streptomyces bullii (Santhanam et al., 2013), which adapted to the alkaline environments with optimum growth in pH of up to 11; Streptomyces aridus (Idris et al., 2017b) is capable of growth in a temperature range between 10 and 40 • C, and S. asenjonii (Abdelkader et al., 2018) and S. leeuwenhoekii (Gran-Scheuch et al., 2018) produced antibacterial metabolites under desert growth conditions. Another dominant group of desert actinobacteria is the genus Geodermatophilus with nine new species identified within the same period. Members of this taxon have demonstrated radiation-resistant capabilities, such as Geodermatophilus pulveris BMG 825 T and Geodermatophilus sabuli BMG 8133 T which are both gamma radiation resistant, whereas Geodermatophilus tzadiensis CF5/2 T is a UV-radiationresistant actinobacterium (Hezbri et al., 2015;Hezbri et al., 2016).

Actinobacterial Diversity in Central and South Asia
Eleven new species of the genera Jiangella, Kribbella, Desertiactinospora, Nonomuraea, Micromonospora, and Streptomyces have been discovered from the Karakum Desert in Central Asia. In South Asia, members of the genera Actinoalloteichus, Agrococcus, Kocuria, Ornithinimicrobium, and Rhodococcus were found from the Lahaul-Spiti Valley cold desert of the Indian Himalayas. Members of the genera Auraticoccus, Arthrobacter, and Motilibacter were recovered from the Cholistan Desert in Pakistan, while Saccharothrix and Yuhushiella were discovered from the Indian Thar Desert. Novel species belonging to the genera Dietzia, Nocardioides, and Streptomyces were isolated from the Kunjam Pass cold desert of the Indian Himalayas, the Thal Desert in Pakistan, and the Kutch saline Desert in India, respectively. S. aburaviensis strain Kut-8 isolated from the saline desert of Kutch is a halotolerant and alkaliphilic actinobacterium that could grow under saline (15% NaCl) and alkaline (pH 9) conditions (Thumar et al., 2010).

Actinobacterial Diversity in the Middle East, North Africa, and South America
In the Middle East, Nonomuraea terrae was isolated from the Anatolia Desert, Turkey, and six new species belong to four genera: Georgenia, Microbacterium, Saccharopolyspora, and Streptomyces, which were discovered from the Saudi Arabia arid desert. Three new species, Georgenia alba SYSU D8008 T (grew in up to 7% NaCl) (Li et al., 2019d), Georgenia deserti SYSU D8004 T (grew in up to 17% NaCl) (Hozzein et al., 2018), and Saccharopolyspora deserti SYSU D8010 T (grew in up to 22% NaCl) , are reported as halotolerant actinobacteria. Representative members of 12 genera were obtained from nine deserts in North Africa. Members of the genera Actinophytocola, Saccharothrix, and Streptosporangium were isolated from the Sahara Desert in Algeria, whereas Citricoccus, Dietzia, Nocardiopsis, and Streptomyces were reported from the Eastern Desert of Egypt. A member of the genus Actinopolyspora, Actinopolyspora mzabensis H55 T isolated from an Algerian Saharan soil, could tolerate up to 32% NaCl (Saygin et al., 2019a). Alkaliphiles include Citricoccus alkalitolerans YIM 70010 T (pH 8-9) (Li et al., 2005), Nocardiopsis alkaliphila YIM 80379 T (pH 9.5-10) (Hozzein et al., 2004), and S. sannurensis WS 51 T (pH 9.5-10) (Hozzein et al., 2011), which were isolated from the Eastern Desert of Egypt. Saccharothrix algeriensis was cultured from a soil sample of palm groves in the Saharan Desert (Zitouni et al., 2004). Geodermatophilus and Promicromonospora strains were recovered from the Sahara Desert in Tunisia. Other genera, namely, Nocardiopsis, Janibacter, Kocuria, Prauserella, and Streptosporangium, were described from the Beni Suef Governorate Desert in Egypt, the arid-saline sediment in Tunisia, the saline-alkaline desert in Egypt, the Béni Isguen Desert, and the Béni Abbès Desert in Algeria, respectively. The alkaliphilic strain of Nocardiopsis benisuefensis WS65 was isolated from the Beni Suef Governorate Desert in Egypt , while a halotolerant actinobacterium Prauserella isguenensis H225 T (grew in up to 25% NaCl) was recovered from the Béni Isguen (Mzab) desert in Algeria (Saker et al., 2015). Twenty-three new species belonging to nine genera (Amycolatopsis, Blastococcus, Geodermatophilus, Lechevalieria, Lentzea, Micromonospora, Modestobacter, Pseudonocardia, and Streptomyces) were reported and described from the Atacama Desert in Chile. One new species, Pseudonocardia nigra ATK03 T , was isolated from the rock surface in the Atacama Desert (Trujillo et al., 2017). Two new species recognized as thermophiles, namely, Amycolatopsis ruanii NMG112 T and Amycolatopsis thermalba SF45 T , could survive under high temperatures (Zucchi et al., 2012a). Another new species, Modestobacter caceserii KNN 45-2b T from the Atacama Desert in Chile, highly adapted to high osmotic stress, cold shock, heat and desiccation, low nutrient, low organic carbon, and high levels of UV radiation (Busarakam et al., 2016b).

Actinobacterial Diversity in Other Regions
Actinomadura namibiensis was isolated from the Namibian Namib Desert in South Africa. Streptomyces netropsis was first discovered in North America in the Baja California Desert of Mexico. The Antarctic Desert at the South Pole yielded one new species of Modestobacter multiseptatus and Williamsia sp., where the former strain was a budding-like psychrophilic actinobacterium isolated from the rock of the Transantarctic Mountains (Mevs et al., 2000). Williamsia sp. D3 was considered as a psychrotolerant, able to grow under at a low temperature of 15 • C (Guerrero et al., 2014). All new species from the Sahara Desert of Chad in Central Africa and the arid Australian Desert in Oceania were classified in the genera Geodermatophilus and Amycolatopsis, respectively. have high drought tolerance ability. Members of the genus Amycolatopsis were described as Amycolatopsis australiensis (Tan et al., 2006), A. deserti (Busarakam et al., 2016a), Amycolatopsis granulosa (Zucchi et al., 2012a), Amycolatopsis thermophila, and Amycolatopsis viridis (Zucchi et al., 2012b). Most of them were recognized as thermophiles that could survive under high temperature, including A. deserti GY024 T , A. granulosa GY307 T , A. thermophila GY088 T , and A. viridis GY115 T , as well as A. ruanii NMG112 T and A. thermalba SF45 T from the Atacama Desert in Chile.

ISOLATION AND TAXONOMIC CHARACTERIZATION OF DESERT ACTINOBACTERIA
A bioprospecting strategy to recover actinobacteria from the desert is summarized in Figure 4. Most procedures involve the selection of samples from the desert, isolation on selective media, and incubation and selection of representative colonies from the isolation plates for further study (Goodfellow, 2010;Goodfellow and Fiedler, 2010;Tiwari and Gupta, 2013). The low occurrence of rare actinobacteria on the isolation plates clearly reflected the limitations of isolation, cultivation, and maintenance using conventional approaches, which fail to provide optimal growth conditions for desert actinobacteria. Thus, a better or improved isolation method is significant for increasing the number of diverse actinobacterial taxa, which remains an effective strategy for natural product discovery (Jensen, 2010;Jensen et al., 2015).

Serial Dilution vs. Sprinkling Technique
In general, selective isolation of actinobacteria from desert samples followed the procedure described by Okoro et al. (2009). Serial dilution is commonly used to prepare desert samples for inoculation. Aliquots of soil suspension prepared from serial dilutions were plated onto the selective isolation media, pre-dried in a laminar flow hood for 15 min (Vickers and Williams, 1987). However, there are certain errors associated with sample preparation using a serial dilution method (Ben-David and Davidson, 2014). The first error is related to the initial sample size. If the sample size is larger or smaller than the nominal diluent, under-dilution or over-dilution errors will occur. Similarly, diluent types, mixing method, and mixing time would also cause the same problems. Other errors may occur due to the pipetting technique. It is possible that a non-representative sample will be transferred to the new dilution and finally inoculated on the isolation plates. These errors would lead to a low number of colonies on the isolation plates. Recently, serial dilution, which is part of the conventional culture procedure (CCP), was clearly demonstrated to have limited selectively for even the isolation of members of the genus Streptomyces, the most dominant desert actinobacteria .
The sprinkling technique is proposed here as an improved isolation method since few reports have found that it is a simpler and less error-prone way to obtain desert actinobacteria compared to the traditional serial dilution technique, especially for the desert taxa, which may prefer to develop in a reducedmoisture environment, similar to that of the desert, rather than a suspension in a diluent. For example, a greater number of actinobacteria were recorded from selective isolation media using the sprinkling inoculation technique as opposed to the suspensions of the desert sample from Atacama Desert as summarized in Table 2 (Xie, 2017). This comparative study was carried out using the same selective media supplemented with the same antibiotics under the same incubation conditions. The number of actinobacteria colonies obtained from sprinkling was 10-20 times higher than that acquired via serial dilution. Higher relative abundance was also observed from the sprinkling technique with actinobacterial count representing 85-100% of total bacteria on the isolation plates. The obtained actinobacteria showed antimicrobial activity that is effective against a panel of bacteria, namely, Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens, Saccharomyces cerevisiae, and Staphylococcus aureus. It is evident that the sprinkling approach clearly provides a higher number of bioactive actinobacteria (141) compared to the serial dilution (97). Again, the number of endophytic actinobacteria acquired from the sprinkling technique is approximately 1.1 times higher than the total population obtained from two improved serial dilution procedures (Qin et al., 2009). Indeed, the isolation medium directly seeded with mineral particles from Atacama Desert soils was found to obtain a higher actinobacterial count than did the serial dilution plates (Idris, 2016). This sprinkling technique allows actinobacterial cells to attach to soil particles in direct contact with the culture media, which increases the isolation efficiency by promoting colony development on the isolation plates (Duddington, 1955;Bailey and Gray, 1989;Qin et al., 2009).

Selective Isolation Media
To maximize the number of actinobacteria, a variety of culture media were employed for the isolation of desert actinobacteria. The effectiveness of the isolation media is closely related to the ecological characteristics of novel actinobacteria from the desert. The media must meet the growth requirements of the target taxa; for example, halophilic strains prefer growth in high-salt-containing media. Selective isolation media resembling the characteristics of the study site increase the success rate of isolation. Carbon and nitrogen sources, growth factors, mineral salts, vitamins, and water are all essential components for the growth of desert actinobacteria on any culture medium (Bonnet et al., 2019). In this aspect, media can be grouped into nutrientrich media and nutrient-poor media. It is worthy to note that the most effective selective isolation media are specifically designed based on the needs and preferences of actinobacteria, notably nutrient requirements and tolerance preferences of the target taxa. Conventional nutrient-rich media have been widely used to cultivate actinobacteria with limited success. Glucose yeast extract (GYE) agar is recommended as the most suitable medium that can result in a high ratio of actinobacterial count The bolded number indicates the highest value in the comparison of serial dilution and sprinkling technique under the same column items. All media were supplemented with cycloheximide and nystatin (each at 25 µg/ml). (Agate and Bhat, 1963). Starch casein agar is preferable, especially for saccharolytic organisms, since it contains starch as the sole carbon source as well as sufficient minerals for protein production (Lee et al., 2014). However, recent studies showed that the normally slow-growing rare genera of Actinobacteria and Proteobacteria failed to grow on commonly used rich media, but growth was observed only from low-nutrient media Salam et al., 2021). Approximately 100 novel actinobacteria have been isolated from nutrient-poor media (Salam et al., 2021). This information strongly suggested that nutrient-poor media are more effective for the growth of desert strains as compared to those previously used nutrient-rich media (Bérdy, 2005;Bredholdt et al., 2007;Hozzein et al., 2008). Nutrient-poor media such as soil extract media and a new minimal medium (MM), which reflect the extreme environmental conditions in the desert with low organic matter content, were superior to currently used isolation media for desert actinobacteria (Hozzein et al., 2008). Similarly, humic acid-vitamin (HV) media are also considered as low-nutrient media and are more effective for the isolation of sporulating actinobacteria than are high-nutrient media (Hayakawa, 2008). Approximately 40 isolation media have been utilized over the last two decades to isolate diverse actinobacterial taxa from the desert (Supplementary Table 3). Reasoner's 2A (R2A) agar was the most often used media for desert actinobacterial isolation, representing 25% of reported genera (13) (Sun et al., 2015), and Williamsia (Guerrero et al., 2014). Other media often employed for the isolation of desert taxa include humic acidvitamin agar and chitin-vitamin agar, which are low-nutrient media comparable to desert environments. Sometimes, media were specially formulated to adjust the nutrient contents to meet the requirements of desert actinobacteria, such as chitin medium, 0.1× tryptic soy agar (TSA) medium, tenfold-diluted trypticase soy broth (TSB) agar, modified 0.3× marine broth agar, and 1/5-strength R2A agar, which were successfully used to recover members of the genera Labedella , Desertimonas , Kineococcus (Liu et al., 2009), Mycetocola (Luo et al., 2012), and Tenggerimyces (Sun et al., 2015). It is worth noting that SM1, SM2, and SM3 agar were specifically designed for the isolation of the Amycolatopsis genus (Tan et al., 2006;Zucchi et al., 2012a), whereas medium A was used to recover the alkaliphilic and alkaline-resistant actinobacteria, such as C. alkalitolerans (Li et al., 2005), Nocardiopsis alkaliphile (Hozzein et al., 2004), and S. sannurensis (Hozzein et al., 2011). In addition, media such as starch casein agar and raffinosehistidine agar were used to promote the growth of desert taxa by employing casein and raffinose (selective macromolecules) as nitrogen and carbon sources, respectively. Saccharothrix tharensis (Thumar et al., 2010) and Yuhushiella sp. (Ibeyaima et al., 2016) were recovered from starch casein agar, while S. atacamensis (Santhanam et al., 2012b) and Streptomyces deserti (Santhanam et al., 2012a) were isolated from raffinose-histidine agar. Recently, a highly selective culture strategy for the isolation of Streptomyces spp. from desert samples was proposed based on the use of minimal medium, actinobacteria isolation agar, and starch casein agar in combination with a cocktail of selective inhibitors . These authors claimed to increase almost fourfold the number and phylotypes of Streptomyces strains isolated from the Gurbantunggut Desert as compared to the conventional approach.

Taxonomic Characterization of Desert Actinobacteria
In general, taxonomic characterization of desert actinobacteria is started with the acquisition of a pure culture of each isolate. Putative actinobacterial colonies from the isolation plates are purified through several rounds of transfer to suitable culture media. Pure isolates of actinobacteria usually develop with different morphological features after being incubated for 2-4 weeks. Morphological characterization of these pure isolated strains was generally observed according to the guidelines proposed by the International Streptomyces Project (ISP), including aerial spore mass, substrate mycelial and diffusible pigments, growth, and formation of melanin pigments (Shirling and Gottlieb, 1966). All isolates were further assigned to singleand multi-membered color groups based on the color of the aerial spore mass and substrate mycelial and diffusible pigments. Representative isolates from each morphotype of these assigned color groups are selected for comparative 16S rRNA gene sequence analysis.
The 16S rRNA gene sequencing analysis is routinely the first step for the identification of desert actinobacteria. Genomic DNA of representative isolates can be extracted by various methods such as the phenol-chloroform extraction (Sagova-Mareckova et al., 2008) or solid-phase DNA extraction method such as the bead beating technique (Fujimoto et al., 2004). Several DNA extraction kits are commercially available. The commonly used kits include the MN DNA extraction kit (Macherey-Nagel, Düren, Germany) (Nithya et al., 2018) and Qiagen Genomic 500 DNA kit (Qiagen, Hilden, Germany) . Nucleotide primers for 16S rRNA gene amplification were summarized in Table 2 including primers 27F and 1492R, which are commonly employed in the study of actinobacteria from deserts.
The information from the 16S rRNA gene sequence is also valuable in delineating actinobacteria from the subspecies to genus levels (Hayashi Sant'Anna et al., 2019). Strains showing less than 98.7% similarity are generally assigned as potential new species (Chun et al., 2018). However, the 16S rRNA genes of members of some closely related species can be too conserved that they cannot be used to differentiate between strains at the species level. Strains of related species with almost identical 16S rRNA gene sequences might belong to different genomic species, as exemplified by members of the genera Amycolatopsis (Sangal et al., 2018) and Streptomyces (Idris et al., 2017b). It is recommended to obtain a genome sequence for comparison to circumscribe novel species. Nevertheless, 16S rDNA sequence data remain invaluable as they can be used to select appropriate reference strains for whole-genome analysis, thereby reducing the number of marker strains that need to be examined.
The description of new taxa is based on application of the polyphasic taxonomic approach based on a combination of genotypic and phenotypic data. Genotypic data are derived from analyses of nucleic acids and phenotypic data from cultural, chemotaxonomic, morphological, nutritional, and other expressed features. Phenotypic tests involve several biochemical properties and ranges of physiological properties such as pH, temperature, and the concentration of NaCl. Enzymatic activities are currently investigated using the API ZYM (bioMérieux) commercial system (Saygin et al., 2019a). For actinobacterial systematics, it is also critical to investigate the chemotaxonomic properties of new species across closely related taxa (Goodfellow et al., 2012). Developments in molecular systematics have been seen by some to question the continued significance of chemosystematics, but this view is unwarranted as the two approaches are complementary. The most valuable chemical characters are derived from analyses of cellular fatty acids, menaquinones, mycolic acids, muramic acid types, peptidoglycan types, polar lipids, and whole-organism sugars (Goodfellow, 1989). Some of these methods provide quantitative or semiquantitative data, as in the case of cellular fatty acid and menaquinone analyses, but others yield qualitative information, as exemplified by muramic acid, mycolic acid, peptidoglycan, phospholipid, and whole-organism sugar determinations.
Whole-genome sequencing provides the most comprehensive and reliable tool for comparative genome (Ekblom and Wolf, 2014). With the advent of whole-genome sequencing, the weakness of 16S rRNA gene sequencing is being compensated. The genome relatedness thresholds were established to determine whether the compared desert strains can be classified into the same taxon. The overall genome-related index (OGRI) is proposed to replace DNA-DNA hybridization for delineating new species (Chun et al., 2018). OGRI can be used to calculate the relatedness between the genome sequences of isolated strains and closely related strain types of a species. In this aspect, average nucleotide identity (ANI) and digital DDH (dDDH) are the two most widely used OGRI. The proposed and generally accepted species boundary for ANI and dDDH values are 95-96 and 70%, respectively (Goris et al., 2007;Richter and Rosselló-Móra, 2009;Meier-Kolthoff et al., 2013;Chun et al., 2018). These ANI and dDDH values represent a high correlation for the species delineation by a DDH cutoff value of 70% (Kim et al., 2014). Currently, genome sequences provided by Illumina (United States), Ion Torrent (Thermo Fisher Scientific, United States), and Pacific Biosciences (United States) platforms have been shown to generate high-quality DNA sequence data that meet the general standards for taxonomic purposes (Chun et al., 2018). It is evident that polyphasic taxonomy will be a standard approach for the taxonomic characterization of desert actinobacteria as it provides a reliable, reproducible, and stable delineation of taxa.

BIOTECHNOLOGICAL APPLICATIONS OF DESERT ACTINOBACTERIA
Desert actinobacteria generally undergo primary screening to have their interesting bioactivity profiles examined in vitro (Figure 4). For example, the obtained actinobacteria are subjected to a standard plug assay against a panel of wildtype microorganisms and B. subtilis reporter strains (Fiedler, 2004). Those exhibiting an extensive inhibition zone against Gram-positive and Gram-negative bacteria, fungi, and yeasts are assigned as potential antibacterial-or antifungalproducing strains. Similarly, plant beneficial traits, such as phytohormone production, siderophore production, and phosphate solubilization can be screened using qualitative assays to determine their agricultural potential (Allali et al., 2019). Potential actinobacteria are selected for the fermentation study of SMs followed by the purification of the obtained bioactive compounds. The chemical structure of the purified compounds will then be elucidated and tested for their biological properties. Desert actinobacteria with the unique ability to produce novel bioactive compounds could also be deposited as patent strains in public culture collections. In this section, we provide evidences for the potential applications of desert actinobacteria in agriculture, the environment, healthcare, and industry.

Healthcare Applications
Actinobacteria isolated from the desert are potential sources of diverse SMs through their unique metabolic pathways, which adapt for survival under extreme habitats. Recently, the extreme biosphere is the focus of research on the discovery of bioactive compounds to combat MDR pathogens and diseases such as cancer, dementia, and epilepsy (Bull and Goodfellow, 2019). During the past two decades, more than 50 novel natural products have been isolated and identified from desert actinobacteria worldwide (Table 3) with potential antiallergic, antibacterial, anticytotoxic, antifungal, anti-inflammatory, antitumor, and antiviral activities. Particularly, members of the genus Streptomyces are responsible for more than half of the reported novel compounds.

Anticancer and Antitumor Compounds
Chaxamycins A-D derived from S. leeuwenhoekii C34 T can be used as anticancer drugs based on their ability to inhibit the intrinsic ATPase activity of heat shock protein 90 (Hsp90) (Rateb et al., 2011a). Another strain, S. leeuwenhoekii C38, produced chaxapeptin, a new lasso peptide with a substantial inhibitory effect in the human lung cancer cell line A549 according to the cell invasion assay (Elsayed et al., 2015). Three antitumor compounds were also derived from S. leeuwenhoekii C38, atacamycins A-C, which moderately inhibited the enzyme phosphodiesterase (PDE-4B2) (Nachtigall et al., 2011). Furthermore, atacamycins A and B showed clear cytotoxic activities against a panel of 42 different human tumor cell lines. Atacamycin A was the most active in cell lines of colon cancer (CXF DiFi), breast cancer (MAXF 401NL), and uterus cancer (UXF 1138L), whereas atacamycin B showed significant antiproliferative activity against colon RKO cells (Nachtigall et al., 2011). Micromonospora chalcea LB4 and LB41 showed antitumor activity against human hepatocellular carcinoma (HepG2) cells (Carro et al., 2019a).

Anti-inflammatory Compounds
Jiangella gansuensis YIM 002 T was collected from Gansu Desert in China and produced seven new compounds, jiangrines A-F and jiangolide, as well as pyrrolezanthine, a known compound (Han et al., 2014). Jiangrines A-E and jiangrine F are pyrrol-2aldehyde derivatives and an indolizine derivative, respectively. All of them, including pyrrolezanthine, demonstrated significant anti-inflammatory activity by inhibiting NO production in LPStreated RAW 264.7 macrophage cells. Jiangolide is a glycolipid with weak cytotoxicity based on a low inhibitory ratio (<20%) of the cell viability assay (Han et al., 2014). Abenquines A-D isolated from Streptomyces sp. DB634 showed moderate antiinflammatory activity against phosphodiesterase type 4 (PDE4b), which can be used to treat inflammatory diseases, such as chronic obstructive pulmonary disease (Schulz et al., 2011).

Antiviral Compounds
Lentzeosides A-F are six new diene and monoene glycosides derived from Lentzea chajnantorensis H45 T isolated from the Atacama Desert (Wichner et al., 2017). These novel compounds clearly inhibited HIV-1 integrase, one of the key enzymes in the HIV replication cycle. Thus, lentzeosides might be used as HIV integrase inhibitors for the treatment of HIV-1 infections, HIV-1 replication, and other virus strains resistant to multi-antiretroviral drugs (Wichner et al., 2017). Nocardia sp. XJ31, isolated from the Xinjiang Desert, generated nine new siderophores (nocardimicins J-R), which were found to inhibit viral infection by binding affinities with the four 3 -RNA pockets of viral polymerases (>90%) .

Antioxidant Compounds
Streptomyces sp. D25, isolated from Thar Desert, Rajasthan, showed antioxidant potential based on free radical scavenging activity using DPPH and nitric oxide assays (Radhakrishnan et al., 2016). It is also moderately effective against biofilmforming bacteria, including Alcaligenes sp. M28, Alcaligenes sp.

Agricultural Applications
Actinobacteria from the desert showed a broad range of plant growth-promoting and biocontrol properties. Their ability to survive under extreme environments allows them to enhance the growth of plants under severe abiotic stresses, especially drought and salinity. Since 2013, 37 actinobacteria from the desert have been reported to have agricultural potential, mostly from members of the genus Streptomyces as summarized in Table 4. All these studies highlight the potential application of desert actinobacteria in agriculture under stress environments.

Plant Growth Promotion
Plant growth-promoting properties displayed by desert actinobacteria include 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase production, auxin production, gibberellic acid (GA) production, indole-3-acetic acid (IAA) production, siderophore production, nitrogen fixation, and P and K solubilization. For example, a high-IAA-producing strain of Kocuria turfanensis 2M4 recovered from a saline desert in India significantly increased the total length and fresh biomass of groundnut after 15 days of germination by pot study (Arachis hypogaea L.) (Goswami et al., 2014). Streptomyces mutabilis IA1 from Saharan soil produced IAA and GA, which are responsible for the promotion of wheat growth after incubation in a phytotronic growth chamber for 10 days (Toumatia et al., 2016). Nocardiopsis dassonvillei MB22 was isolated from the Algerian Sahara soil and can stimulate the growth of durum wheat seedlings (shoot and root lengths and dry weight) by a variety of properties (chitinolytic activity, hydrogen cyanide production, IAA production, siderophore production, and inorganic phosphate solubilization) (Allali et al., 2019). Three plant growth-promoting Streptomyces isolated from the desert plant Pteropyrum olivieri could enhance the yield and biochemical contents of sunflower in greenhouse and field experiments under normal conditions (Zahra et al., 2020). These streptomycetes could also improve salt and drought tolerance in inoculated sunflower seedlings. In addition, they can act as plant probiotics by supplying the host plant with three major traits: acquisition of nutrients, growth hormone, and stress tolerance. Microbacterium sp. WLJ053 and Streptomyces sp. WLJ079 from the rhizosphere of A. sparsifolia harbored a nitrogen-fixation gene nif H, which improved maize growth by increasing stem and root lengths, fresh and dry weights after 1 month planting, and cultivation in the greenhouse (Wang et al., 2017). In addition, S. netropsis A-ICA from Larrea tridentata in the Baja California Desert of Mexico enhanced root elongation and development of wheat by the production of IAA, siderophores, and GA and phosphate solubilization after 4 days of germination in semisolid plates (Abdelmoteleb and González-Mendoza, 2020).

Mitigation Potential for Abiotic Stress in Plants
Streptomyces sp. AC5 from the semi-arid environment of Saudi Arabia could mitigate the negative effects of drought on the growth and physiology of maize, discovered from 6 weeks of cultivation in a controlled greenhouse (Selim et al., 2019). This IAA-and siderophore-producing Streptomyces sp. AC5 positively enhanced the growth and drought tolerance ability of maize by reducing H 2 O 2 accumulation and lipid peroxidation through the production of antioxidants (total ascorbate, glutathione, tocopherols, phenolic acids, and flavonoids) and compatible solutes (sucrose, total soluble sugar, proline, arginine, and glycine betaine). The IAA and siderophores were suggested to promote root architecture and water and nutrient uptake from drought-affected soil (Selim et al., 2019). Similarly, Cellulosimicrobium sp. JZ28 was isolated from Panicum turgidum in the Saudi Arabia Desert, and its whole-genome sequence indicated that several genes were responsible for protecting the plant from environmental stresses, such as the ability to synthesize osmoprotectants and volatile compounds in order to withstand abiotic and biotic stresses (Eida et al., 2020).

Biocontrol Potential
Streptomyces mutabilis IA1 from Saharan soil exhibited biocontrol property to decrease severity (79.6%) and reduce occurrence (64.7%) of fungal infection caused by F. culmorum evaluated from 10 days young wheat (Triticum aestivum L.) seedlings in a phytotronic growth chamber (Toumatia et al., 2016). N. dassonvillei MB22, a powerful antifungal producing strain isolated from Algerian Sahara soil, could be used as a biocontrol agent to ensure crop health (Allali et al., 2019). This strain has the potential for controlling several soil-borne phytopathogens (

Industrial and Environmental Application
To adapt for living in the extreme arid ecosystems, various functional enzymes were synthesized by actinobacteria, and these enzymes can be applied for industrial and environmental uses. Those studies shown below provide supporting evidence for potential applications of desert actinobacteria in the environment and industry.

Pentachlorophenol Remediation
Pentachlorophenol (PCP) is a commonly utilized technique in some industries, such as the preservation of wood and leather (Kao et al., 2004). However, PCP is also toxic, and its exposure can induce acute pancreatitis, cancer, immunodeficiency, and neurological problems, as well as inhibiting oxidative phosphorylation (Sai et al., 2001;Shen et al., 2005). A halotolerant Janibacter sp. FAS23 strain obtained from arid and saline Tunisia terrain can degrade PCP (Khessairi et al., 2014). Strain FAS23 was able to degrade PCP up to 300 mg/L and could be used for PCP bioremediation in PCP-contaminated environments.

Industrial Potential
Two new oxidative enzymes, type I Baeyer-Villiger monooxygenases (BVMOs), industrial potential biocatalysts were discovered from S. leeuwenhoekii C34, isolated from Atacama Desert. These new BVMOs enzymes with high melting temperature (45 • C) and water-miscible cosolvents tolerance were capable of NADPH-dependent BV oxidation activity on ketones, sulfoxidation activity on sulfides (Gran-Scheuch et al., 2018). In Saudi Arabia, Streptomyces fragilis DA7-7 synthesized a thermostable α-amylase, an important enzyme with commercial potential in industries, including brewery, detergent, paper, food, starch saccharification and pharmaceuticals. (Nithya et al., 2017). Am-fluorinase, another thermostable enzyme, was found in A. mzabensis from Saharan soil in Algeria (Sooklal et al., 2020). This enzyme is responsible for incorporating fluorine into organic molecules to improve the bioactive and biophysical characteristics of compounds and has been widely used in the agrochemical, material and pharmaceutical industries. The Am-fluorinase from A. mzabensis catalyzed a C-F bond and displayed great thermostability with the optimum temperature at 65 • C. Cellulosimicrobium sp. JZ28, isolated from P. turgidum also contains genes encoding for β-glucosidases enzymes (Eida et al., 2020). This enzyme could be applied to extract the juice and liberate aroma from wine grapes by hydrolyzing bitter compounds, for example, it can enhance the flavor of fruit juice, tea, and wine in food processing industries (Singh et al., 2016).

CONCLUSION AND FUTURE PERSPECTIVES
Diverse actinobacteria from the desert are undoubtedly potential resources for biotechnology. These actinobacteria which thrive under such extreme environmental conditions, exhibit the diversity and their exceptional adaptability from specialized metabolisms. This review explored 129 new species including alkaliphiles, halotolerant, thermophile and psychrotolerant from 35 deserts in the past two decades. Several species showed potential applications in biotechnology in particular bioactive compounds production, biocontrol properties, functional enzymes and plant growth promotion. The survival mechanisms of actinobacteria under extensive environmental stress in the desert offer tremendous possibilities to explore novel bioactive compounds with unique biosynthesis pathways. It is strongly supporting the view that gifted desert actinobacteria with their bioactive potential provide beneficial appropriate solutions to triumph over the increasingly serious threats from MDR pathogens, agricultural stress and environmental problems.
To recover untapped diversity of culturable actinobacteria from desert, it is extremely important and urgently need for develop improved techniques for selective isolation of target taxa. The progress of actinobacterial diversity depends on the development of such isolation methods which can reflect physicochemical characteristics of the desert environments. Growth of desert actinobacteria is mainly influenced by several physicochemical factors, such as the cation exchange capacity (CEC), the carbon and nitrogen sources, water retention capacity, hydrogen-ion concentration (pH) and temperature . To date, studies have revealed that the efficiency of actinobacterial isolation methods was positively related to the choices of selective media, supplemented inhibitors, inoculation techniques and incubation conditions, which mimics desert environments (Goodfellow, 2010;Goodfellow and Fiedler, 2010;Tiwari and Gupta, 2013). Selective media provide nutrient sources require for the growth and proliferation of target actinobacteria with the help of inhibitors to suppress the growth of unwanted bacteria. Most desert actinobacteria are slowgrowing actinobacteria, with a preference for poor nutrient media over nutrient rich media . The supplement of selective antibiotics was significantly promoted the isolation of desert taxa by sharply reduced the number of unwanted bacteria represented by the genus Bacillus. Media supplemented with these antibiotics far exceeded in obtaining the target actinobacteria than media without supplementation . In addition, a higher number of isolates were recorded from the isolation media using the sprinkling technique for inoculation as compared with those corresponding plates prepared from the traditional serial dilution method (Idris, 2016;Xie, 2017). As opposed to the isolation plates seeded with soil suspensions, sprinkling technique allowed the mineral particles to be in direct contact with the nutrients in the media, which may stimulate spore germination and improve the growth of actinobacteria. More diversity was recovered from mineral particles inoculated onto selective media supplemented with inhibitor using sprinkling technique as exemplified by Idris (2016) and Xie (2017). Therefore, it is strongly recommended to use the sprinkling technique for the isolation of actinobacteria from desert associated samples.
In addition to culture-dependent studies, next-generation sequencing techniques and metagenomics are widely used in the identification and characterization of actinobacteria to gain an understanding of their diversity and functions in the desert. However, most desert microorganisms cannot be cultured as exemplified by only 1% of them are culturable (Martiny, 2019). Whole-genome sequences seem to be an effective way to resolve these taxonomic bottlenecks with increasing utilization in systematic studies. It provides a deep insight into the ecology and biotechnological potential of desert species. Currently, 16,763 reference genomes are available in the database (Shi et al., 2021). With the increasing availability of genome sequences, the information regarding genes and their functions provides insights into the metabolic potential of desert actinobacteria, which will greatly promote their biotechnology applications. A culture-enriched metagenomic approach named PLate Coverage Algorithm (PLCA) is developed based on the use of 16S rRNA gene sequencing of cultureenriched plates and shotgun metagenomics to identify the microbial community and their functions, which has been succeeded to recover bacteria including actinobacteria from the cystic fibrosis (Whelan et al., 2020). The PLCA improves the recovery of microbial diversity in the sample and provides a better understanding of the mechanisms between microbial communities and the host environment. This method can be used on any low-abundance microbial community in particular low-abundance actinobacterial taxa from desert, such as Desertiactinospora, Tenggerimyces. Another method for recovering unculturable actinobacteria is the cooperation of 16S rRNA gene metagenomics and commercially available media (Ito et al., 2019). These authors suggested that selective features of media are significantly influenced the recovery of slowgrowing taxa on the isolation plates. Successful isolation of novel actinobacteria from commercially available media suggested that uncultured actinobacteria are potentially culturable. This method highlights the high possibility of the recovery of low-abundance taxa in laboratory culture. Besides, computational techniques are continuedly developed since several new algorithms, tools and databases are becoming available, aiming to explore both actinobacterial diversity, their functions and biotechnological potential (Medema, 2021). Several bioinformatics tools are designed specifically for the prediction of bioactive compounds with novel chemical structures from the whole genome sequences (Mikulak-Klucznik et al., 2020;Stokes et al., 2020). An effective biosynthetic pathway for such new compounds can be selected and mined through these genomic data for further engineering purposes. These exciting improvements will undoubtedly provide a tool for the recovery of novel taxa, their ecological functions and the discovery of un-hitherto biotechnological values of these desert actinobacteria. The more comprehensive knowledge should be built upon the principle of "embrace the genome" (Whitman, 2014), which would provide an immensely richer understanding of the biology of actinobacteria in desert environments.

AUTHOR CONTRIBUTIONS
FX wrote the first draft. WP conceived the idea and supervised FX. FX and WP revised the manuscript. Both authors contributed to the article and approved the submitted version.