Marine Actinomycetes Research Articles

Unveiling the Pharmacological Significance of Marine Streptomyces violaceusniger KS20: Isolation, Characterization, and Assessment of Its Biomedical Applications.

Marine actinomycetes represent a highly favorable source of bioactive compounds and have been the mainstay of much research in recent years. Recent reports have shown that marine Streptomyces sp. can produce compounds with diverse and potent biological activities. Therefore, the key objective of the study was to isolate and screen a potential actinomycete from marine ecosystems of Devbagh and Tilmati beaches, Karwar. Streptomyces sp. KS20 was characterized and the ethyl acetate extract (EtOAc-Ex) was screened for biomedical applications. Streptomyces sp. KS20 produced grayish-white aerial and pale-yellow substrate mycelia and revealed an ancestral relationship with Streptomyces violaceusniger. Optimum growth of the organism was recorded at 30 °C and pH 7.0. The metabolite profiling of EtOAc-Ex expressed the existence of several bioactive metabolites, whereas the functional groups were indicated by Fourier transform infrared (FTIR) spectroscopy. A considerable antioxidant activity was shown for EtOAc-Ex with IC50 of 92.56 μg/mL. In addition to this, Streptomyces sp. KS20 exhibited significant antimicrobial properties, particularly against Escherichia coli, where a zone of inhibition measuring 36 ± 0.83 mm and a minimum inhibitory concentration (MIC) of 3.12 µg/mL were observed. The EtOAc-Ex even revealed significant antimycobacterial potency with IC50 of 6.25 μg/mL. Finally, the antiproliferative potentiality of EtOAc-Ex against A549 and PC-3 cell lines revealed a constant decline in cell viability while raising the concentration of EtOAc-Ex from 12.5 to 200 μg/mL. The IC50 values were determined as 94.73 μg/mL and 121.12 μg/mL for A549 and PC-3 cell lines, respectively. Overall, the exploration of secondary metabolites from marine Streptomyces sp. KS20 represents an exciting area of further research with the potential to discover novel bioactive compounds that could be developed into therapeutics for various medical applications.

Bioactive Metabolites from Terrestrial and Marine Actinomycetes.

Actinomycetes inhabit both terrestrial and marine ecosystems and are highly proficient in producing a wide range of natural products with diverse biological functions, including antitumor, immunosuppressive, antimicrobial, and antiviral activities. In this review, we delve into the life cycle, ecology, taxonomy, and classification of actinomycetes, as well as their varied bioactive metabolites recently discovered between 2015 and 2023. Additionally, we explore promising strategies to unveil and investigate new bioactive metabolites, encompassing genome mining, activation of silent genes through signal molecules, and co-cultivation approaches. By presenting this comprehensive and up-to-date review, we hope to offer a potential solution to uncover novel bioactive compounds with essential activities.

Antibiotic Potential of Marine Actinomycetes of the Genera <i>Streptomyces</i> and <i>Nocardiopsis</i>

Due to the emergence of antibiotic resistance in pathogenic microorganisms, it is urgent to search for producers of new antimicrobial metabolites. Actinomycetes are gram-positive mycelial bacteria that produce a large number of antibiotics used in medicine and the agro-industrial complex. Currently, researchers are focused on the search for actinomycetes in ecological niches such as freshwater and marine reservoirs, zones with extreme natural conditions (permafrost soils, glaciers, desert, saline soils, etc.). In this study, cultures of marine actinomycetes were restored after 15 years of storage under vaseline oil. It was shown that all strains retained viability and antibiotic activity at a high level. Based on the results of 16S rRNA gene sequence analysis, the species were identified as: Streptomyces sampsonii 6N, Streptomyces sampsonii 8N, Streptomyces sampsonii 521N, Streptomyces halstedii 22N, Streptomyces brevispora 12N, Streptomyces hirsutus 23N, Streptomyces niveus 14N, Nocardiopsis alba 24N, Nocardiopsis alba 73N, Nocardiopsis alba 85N, Nocardiopsis alba 106N, Nocardiopsis alborubida 722N, Nocardiopsis umidischolae 755N, Nocardiopsis umidischolae 763N. These strains of actinobacteria possessed significant antibiotic activity against the following pathogens: Micrococcus luteus ATCC 9341, Staphylococcus aureus INA 00985, Bacillus subtilis ATCC 6633, Staphylococcus aureus INA 00761 (MRSA — Staphylococcus aureus), Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Pectobacterium carotovorum VKM-B1247, Saccharomyces cerevisiae INA 01042, Candida albicans ATCC 14053, Aspergillus niger ATCC 16404, Aspergillus fumigatus CPB F -37, Fusarium solani VKPM F-890, Fusarium oxysporum VKPM F-148. Therefore, this study evaluated the marine actinomycetes can be potential producers of the novel antibiotics.

Jejucarbosides B-E, Chlorinated Cycloaromatized Enediynes, from a Marine Streptomyces sp.

Four new chlorinated cycloaromatized enediyne compounds, jejucarbosides B-E (1-4), were discovered together with previously-identified jejucarboside A from a marine actinomycete strain. Compounds 1-4 were identified as new chlorinated cyclopenta[a]indene glycosides based on 1D and 2D nuclear magnetic resonance, high-resolution mass spectrometry, and circular dichroism (CD) spectra. Jejucarbosides B and E bear a carbonate functional group whereas jejucarbosides C and D are variants possessing 1,2-diol by losing the carbonate functionality. It is proposed that the production of 1-4 occurs via Bergman cycloaromatization capturing Cl- and H+ in the alternative positions of a p-benzyne intermediate derived from a 9-membered enediyne core. Jejucarboside E (4) displayed significant cytotoxicity against human cancer cell lines including SNU-638, SK-HEP-1, A549, HCT116, and MDA-MB-231, with IC50 values of 0.31, 0.40, 0.25, 0.29, and 0.48 μM, respectively, while jejucarbosides B-D (1-3) showed moderate or no cytotoxic effects.

Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by Kelch-like ECH-associated protein 1 (Keap1) alkylation plays a central role in anti-inflammatory therapy. However, activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified. Deoxynyboquinone (DNQ) is a natural small molecule discovered from marine actinomycetes. The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1. DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo. The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α, β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine. DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway. Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation. The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry. DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489 (Cys489) on Keap1-Kelch domain, ultimately enabling the activation of Nrf2. Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α, β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain, suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

A Potential Source of Anti-Cancer Drugs: Marine Raw Materials

Marine populations serve as a repository for novel bioactive metabolites with a wide range of chemical configurations. The influence of marine species is highlighted in this review, with a focus on marine plants, algae, bacteria, actinomycetes, fungi, sponges, and soft corals. Disease ailment patterns are shifting, and new diseases are arising as a result of changing settings. The massive increase in the world’s population has put a strain on the available drug resources. As a result, drug companies are constantly on the search for fresh resources to help them develop effective and safe drugs to meet the growing demands of the global population. The marine environment contains an abundance of various materials for developing novel medications to treat important diseases such as cancer. Cancer is still one of the deadliest diseases on the planet. New medications with novel modes of action are desperately needed, thus much research has been done on new anticancer treatments derived from natural sources, including plants, microorganisms, and marine organisms. The anti-cancer benefits of marine natural products in in vitro and in vivo research were initially discussed, as well as their activity in tumor prevention and associated compoundinduced apoptosis and cytotoxicities.

Iseoic acids and bisiseoate: three new naphthohydroquinone/naphthoquinone-class metabolites from a coral-derived Streptomyces.

Two new naphthohydroquinone derivatives designated iseoic acids A (1) and B (2) and a new symmetrical glycerol bisester of naphthoquinonepropanoic acid designated bisiseoate (3) were isolated from the culture extract of a marine-derived actinomycete Streptomyces sp. DC4-5. The structures of 1-3 were determined by analyzing one- and two-dimensional NMR data and MS analytical data. The absolute configurations were determined by NOESY analysis and the phenylglycine methyl ester (PGME) method for 1 and by considering the structural similarity and biosynthesis for 2 and 3. Compound 3 exhibited modest cytotoxicity against P388 murine leukemia cells with an IC50 value of 19 μM.

Development of a drug discovery approach from microbes with a special focus on isolation sources and taxonomy.

After the successful discoveries of numerous antibiotics from microorganisms, frequent reisolation of known compounds becomes an obstacle in further development of new drugs from natural products. Exploration of biological sources that can provide novel scaffolds is thus an urgent matter in drug lead screening. As an alternative source to the conventionally used soil microorganisms, we selected endophytic actinomycetes, marine actinomycetes, and actinomycetes in tropical areas for investigation and found an array of new bioactive compounds. Furthermore, based on the analysis of the distribution pattern of biosynthetic gene clusters in bacteria together with available genomic data, we speculated that biosynthetic gene clusters for secondary metabolites are specific to each genus. Based on this assumption, we investigated actinomycetal and marine bacterial genera from which no compounds have been reported, which led to the discovery of a variety of skeletally novel bioactive compounds. These findings suggest that consideration of environmental factor and taxonomic position is critically effective in the selection of potential strains producing structurally unique compounds.

Lipase-producing Marine Actinomycetes Having Potential to Degrade PET Film

Currently, the study and the development of plastic degradation are receiving great attention since it could potentially be applied to plastic degradation. Owing to its environmentally benign nature, the enzymatic process of plastic degradation is highly desired. Polyethylene terephthalate (PET) is one of the most common plastic materials. The degradation of PET was possible by the treatment of the three hydrolases, namely cutinase, lipase, and esterase. On the other hand, marine actinomycetes, which are commonly found to associate with other organisms such as a sponge or residing in a unique environment such as marine sediment, could be a great source of valuable metabolites and enzymes. For that reason, in this study, six isolates of marine actinomycetes showing lipase activity were tested for PET-film degradation. The PET-film degradation was performed by incubating the isolates in a liquid media supplemented with PET films for 14 days. The resulting PET films were then subjected to XRD, FTIR, and SEM analysis. Despite of the decrease in crystallinity of PET-film which was only observed in treatment with isolate BLC 17-1, the FTIR analysis revealed that all absorbances, which are related to PET functionalities, were reduced. Further analysis by SEM showed that the surface of PET films treated with isolates was damaged, indicating degradation of the films. According to the results, it is concluded that the six isolates of marine actinomycetes have the potential to be applied to PET-film degradation.

Efficacy of the Fruit and Vegetable Peels as Substrates for the Growth and Production of α-Amylases in Marine Actinobacteria.

Enzymes from haloalkaliphilic microorganisms have recently focused attention on their potential and suitability in various applications. In this study, the growth and production of extracellular amylases in the marine actinomycetes, using kitchen waste as the raw starch source, have been investigated. Actinobacteria were isolated from the seawater of the Kachhighadi Coast near Dwarika, Gujarat. Seven Actinobacterial isolates of pre-monsoon, monsoon, and post-monsoon seasons belonging to different strains of Nocardiopsis genera were screened and selected for amylase production. The amylase production was initially assessed on the solid media supplemented with the extracts of different fruits and vegetable peels as a substrate by agar plate assay. The strains Kh-2(13), Kh-2(1), and Kh-3(12) produced maximum amylase with potato peel as a substrate, while no significant differences were found with the media containing other peels. Nevertheless, all strains produced amylases at a significant level with other raw substrates as well. For the optimization of the growth and enzyme production, the selected two isolates Kh-2(13) and Kh-3(12) of the monsoon and winter seasons were cultivated in a liquid medium under the submerged fermentation conditions, with potato peel as a substrate. In both organisms, the optimum amylase production was observed in the stationary phase of growth. For amylase production, the effect of different physical and chemical parameters was evaluated. The optimum growth and amylase production was achieved in 2% inoculum size, at pH 8.0, 28℃, and 5% salt concentration. On the basis of the amylase production index (API) (a ratio of the amylase units and cell growth), both isolates produced significant amylase with the only extract of potato peels, without any other supplements. The trends further indicated that while additional complex sources, such as yeast extract and peptone can enhance the cell growth of the actinobacteria, the amylase production remained unaltered. The study projects the significance of waste raw materials for the production of enzymes in extremophilic microorganisms.

Biological Control of sheath blight disease in rice using Marine Actinomycetes (Streptomycetes rochei) AMET A311 strain

The soil samples were taken from the rhizome soil of coastal sand dune plants along the Hare islands, Tuticorin, East Coast of Tamil Nadu, in order to isolate an efficient antifungal marine actinomycetes. A total of 70 actinomycetes were isolated from the samples collected. Based on colony morphology, aerial mass color, melanoid pigments, reverse side pigments, soluble pigments, spore chain morphology and spore surface, 62 of the 70 isolates were identified as distinct. Fifty isolates from the 62 distinct colony were chosen for the antifungal activity based on their capacity to endure salt concentrations over 1M. Rhizoctonia solani, a fungus pathogen, was tested against each of the 50 identified strains. Rhizoctonia solani, a fungus, was resistant to about 36% of the isolates. AMET 307, AMET 308 and AMET 307, AMET 311 and AMET 315 exhibited the highest level of antifungal activity against Rhizoctonia solani. Using 16s rRNA sequencing, this effective antifungal strain was further identified as the Streptomycetes rochei AMET 311 strain (KT334600).

Multipotential Secondary Metabolites from Nocardiopsis dassonovillei of Marine Actinomycetes and their In Silico studies

ABSTRACT: Actinomycetes are one of the important secondary metabolite producers. Researchers focused on the exclusive marine areas for isolation and identification of marine actinomycetes. The present study focused on the isolation and identification of Nocardiopsis dassonovillei (ON627850) from TS Pettai region. The potential strainTSP1 showed effective antibacterial activity against Haemophilus influenza. TSP1 isolates showed IC50 value of 75.22 μg/ml effective antioxidant activity determined by DPPH assay. Cytotoxicity assay results were noted for the ethyl acetate extract of TSP1 screened against oral cancer cell lines (KB). The spectral characterization studies of UV, FT-IR and GC-MS results identified the compound 2,4-di-tert-butylphenol. The multi-potential 2,4-di-tert-butylphenol compound finally docked with KB cell lines protein for drug discoveries.

Exploration and Biorefinery Antimicrobial Agent through Solid State Fermentation from Indonesia’s Marine Actinomycetes

This study aimed to obtain novel bioactive compounds derived from actinomycetes associated with marine biota from the coast of Indonesia. Actinomycetes have been identified as a potential source of bioactive compounds through enzymatic fermentation. In order to obtain bioactive compounds from the results of the biorefinery process, cultivation was performed by solid state fermentation (SSF) on shrimp shell waste medium. The inhibitory activity against pathogenic microorganisms was measured based on the optical density of samples from Gorontalo and Buleleng, Bali, Indonesia. Six isolates had a clear zone as an indicator of the chitinase activity of chitinase enzymes. The SSF extract, obtained after 14 days of incubation, was assayed for its antimicrobial activity by the 96-well plate microtiter method. Among the six isolates, isolate 19B19A1 had antibacterial and antifungal activity against Staphylococcus aureus and Malassezia globosa, respectively. DNA analysis indicated that the 19B19A1 isolate was Streptomyces tritolerans 19B19A1 and that its extract contained an alkaloid component that played a role in antimicrobial activity. These results indicate that shrimp shells can be used as a nutrient-rich alternative culture medium for actinomycetes. This study is expected to become a source of information related to biorefinery, especially in the exploration of bioactive compounds produced by actinomycetes.

Isolation and structure elucidation of aromatic polyketides from marine actinomycete with antibiofilm activity against Staphylococcus aureus and Escherichia coli

Isolation and structure elucidation of aromatic polyketides from marine actinomycete with antibiofilm activity against Staphylococcus aureus and Escherichia coli

Anti-biofilm efficacy of marine actinomycete mediated zinc oxide nanoparticles increased the intracellular damages in biofilm forming K. pneumoniae

In this study, zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized by marine endophytic actinomycete Streptomyces coeruleorubidus (S. coeruleorubidus). In result, the 380 nm spectrum of the synthesized peak was confirmed as ZnO NPs. Uniform sized nanoparticles that particle size was distributed in the range from 6 nm to 195 nm. The exact ZnO NPs morphology was clearly shown by transmission electron microscope analysis. In addition, the single crystalline or poly crystalline or amorphous nature of the ZnO NPs was clearly indicated by the result of SAED. The XRD diffraction and EDX values were more high and confirmed as ZnO NPs. Further, the antibiofilm properties of the biosynthesized ZnO NPs was exhibited 32 mm zone of inhibition against biofilm producing K. pneumoniae at 1000 µg/mL concentration. The 98% of biofilm eradication in K. pneumoniae was observed after treatment with ZnO NPs at 24 h. Furthermore, the survival fitness of the biofilm cells were degraded very high rate at 1000 µg/mL concentration of ZnO NPs. Altogether, the present result was proved that the biosynthesized ZnO NPs was very effective against biofilm forming K. pneumoniae at very low concentration, and it is an alternative drug candidate molecule in future drug discovery process.

Xylanopectinolytic enzymes by marine actinomycetes from sediments of Sarena Kecil, North Sulawesi: high potential to produce galacturonic acid and xylooligosaccharides from raw biomass

BackgroundActinomycetes isolated from marine habitats are known to have the potential for novel enzymes that are beneficial in the industry. In-depth knowledge is necessary given the variety of this bacterial group in Indonesia and the lack of published research. Actinomycetes isolates (BLH 5-14) obtained from marine sediments of Sarena Kecil, Bitung, North Sulawesi, Indonesia, showed an ability to produce pectinase and xylanase that have equal or even higher potential for pectic-oligosaccharides (POS) and xylooligosaccharides (XOS) production from raw biomass than from commercial substrates. This study’s objective was to characterize both enzymes to learn more for future research and development. ResultsPectinase had the highest activity on the 6th day (1.44±0.08 U/mL) at the optimum pH of 8.0 and optimum temperature of 50 °C. Xylanase had the maximum activity on the 6th day (4.33±0.03 U/mL) at optimum pH 6.0 and optimum temperature 60 °C. Hydrolysis and thin layer chromatography also showed that pectinase was able to produce monosaccharides such as galacturonic acid (P1), and xylanase was able to yield oligosaccharides such as xylotriose (X3), xylotetraose (X4), and xylopentaose (X5). BLH 5–14 identified as the genus Streptomyces based on the 16S rDNA sequences and the closely related species Streptomyces tendae (99,78%). ConclusionsIn the eco-friendly paper bleaching industry, Streptomyces tendae has demonstrated the potential to create enzymes with properties that can be active in a wide range of pH levels. The oligosaccharides have the potential as prebiotics or dietary supplements with anti-cancer properties. Further research is needed to optimize the production, purification, and development of the application of pectinase and xylanase enzymes produced by Actinomycetes isolates.

Antibacterial activity of a novel compound isolated from Bacillus licheniformis for treating bacterial infections in fishes: An in-silico approach.

Aeromonas hydrophila is a fish pathogen which is widely associated with diseases related to freshwater fishes. Vibrio parahemolyticus is a major globally emerging marine pathogen. Seven novel compounds were extracted from the ethyl acetate extract of Bacillus licheniformis, a novel marine bacterium isolated from marine actinomycetes. The compounds were identified using Gas Chromatography-Mass Spectroscopy (GC-MS). Only one bioactive compound having potent antibacterial activity was virtually screened to understand its drug-like property according to Lipinski's rule. The core proteins, 3L6E and 3RYL from the pathogens, A. hydrophila and V. parahemolyticus were targeted for drug discovery. In the present in-silico approach, Phenol,2,4-Bis(1,1-Dimethylethyl) a potent bioactive compound present in Bacillus licheniformis was used to prevent the infection due to the two pathogens. Further, using this bioactive compound, molecular docking was done to block their specific target proteins. This bioactive compound satisfied all the five rules of Lipinski. Molecular docking result revealed the best binding efficacy of Phenol,2,4-Bis(1,1-Dimethylethyl) against 3L6E and 3RYL with -4.24kcal/mol and -4.82kcal/mol, respectively. Molecular dynamics (MD) simulations were also executed to determine the binding modes as well as the stability of the protein-ligand docking complexes in the dynamic structure. The in vitro toxicity analysis of this potent bioactive compound against Artemia salina was carried out, revealing the non-toxic nature of B. licheniformis ethyl acetate extract. Thus, the bioactive compound of B. licheniformis was found to be a potent antibacterial agent against A. hydrophila and V. parahemolyticus.

Pyrrole-Containing Alkaloids from a Marine-Derived Actinobacterium Streptomyces zhaozhouensis and Their Antimicrobial and Cytotoxic Activities.

Two new alkaloids, streptopyrroles B and C (1 and 2), were discovered through a chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces zhaozhouensis, along with four known analogs (3-6). The structures of the new compounds were elucidated by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and a comparison of their experimental data with literature values. The new compounds were evaluated for their antimicrobial activity by standard broth dilution assay, and the tested compounds showed significant activity against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 0.7 to 2.9 µM, and kanamycin was used as a positive control with MIC values ranging from <0.5 to 4.1 µM. Additionally, 1, 3, and 5 were evaluated for their cytotoxicity against six tumor cell lines by sulforhodamine B (SRB) assay, and these compounds displayed cytotoxic activities against all the tested cell lines, with concentration causing 50% cell growth inhibition (GI50) values ranging from 4.9 to 10.8 µM, while a positive control, adriamycin, showed GI50 values of 0.13-0.17 µM.

Anti-inflammatory Oleanane-Type Triterpenoids Produced by Nonomuraea sp. MYH522 through Microbial Transformation.

Eleven oleanane-type triterpenoids named soyasapogenols B1-B11 have been obtained unexpectedly from a marine actinomycete Nonomuraea sp. MYH522. Their structures have been determined by extensive analysis of spectroscopic experiments and X-ray crystallographic data. Soyasapogenols B1-B11 exhibit subtle differences in the positions and degrees of oxidation on an oleanane skeleton. The feeding experiment suggested that soyasapogenols might be derived from soyasaponin Bb through microbial-mediated conversion. The biotransformation pathways from soyasaponin Bb to five oleanane-type triterpenoids and six A-ring cleaved analogues were proposed. The assumed biotransformation involves an array of reactions including regio- and stereo-selective oxidation. These compounds alleviated the 5,6-dimethylxanthenone-4-acetic acid-induced inflammation in Raw264.7 cells via the stimulator of interferon genes/TBK1/NF-κB signaling pathway. The present work provided an efficient approach for rapid diversification of soyasaponins and for developing food supplements with potent anti-inflammatory effects.

Role of Actinomycetes from different habitats as a potential source for the production of novel bioactive compounds: A Review

These days, actinomycetes are a good source of producing bioactive compounds that are used for drug discovery with antibacterial, antifungal, antiviral, enzyme inhibition, anticancer and anti-protozoan potential for industrial or medical purposes. Lots of research have been conducted on marine actinomycetes for their potential activity. Extreme environmental sources are less explored for actinomycetes as a potential organism for bioactive compounds potentially because of the difficulties in laboratory handling conditions. Extreme natural habitats are one of the best sources of bioactive compounds produced from actinomycetes as the hot spring area is the origin of thermophilic bacteria as well as actinomycetes. Actinomycetes are observed as a powerhouse to be the bulk patent origin for the production of novel bioactive compounds. In recent years, bioactive compounds from actinomycetes are becoming very useful for new drug discovery and commercial purposes. Actinomycetes species are laborious to cultivate and the production of their desirable metabolites is insufficient in terms of cost and quantity. However, bioinformatics, nucleotide sequencing and metagenomics next-generation tools are continuously developing. The natural hot spring ecosystem can also allow the useful new origin of bioactive compounds diversity with innovative new actinomycetes species compared to the marine ecosystem. We need to focus on all new possible terrestrial ecosystems for discovering novel actinomycetes species to derive potential bioactive compounds from them.