PDF | Marine actinomycetes were isolated from sediment samples collected from of eight mangrove species of Pitchavaram mangrove ecosystem. Abstract: Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. Driven by the discovery of novel natural products from. We conclude that actinomycetes isolated from mangrove habitats are a Similarly, potent and selective protein tyrosine phosphatase 1B.
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Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem mangrovs becoming a hot spot for natural product discovery and bioactivity survey.
Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes.
Attractive structures such as salinosporamides, protoens and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants.
Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery. In the past few decades, repeated isolation of known natural products and a mxngrove hit-rate of novel compounds from heavily investigated terrestrial microorganisms have limited the development of new and effective drugs for treating ever increasing human diseases [ 1 ].
On the other hand, the arising antibiotic-resistant pathogens present an urgent requirement for new bioactive compounds discovery. Hence, more and more researchers have switched over to new or extreme environments for novel pharmaceutical compounds such as deep oceans [ 23 ], deserts [ 4 ], polar areas [ 5 ] and mangroves [ 6 ]. Mangrove is a high moisture, high salinity, and hypoxia tolerant ecosystem [ 9 ] which breeds many kinds of novel microorganisms and plants that have been a rich source of bioactive natural products [ 10111213 ].
Mangrove trees have been acknowledged as medicinal plants by the local people. About 70 mangrove plant species of 27 genera have been reported and extracts from these plants showed antimicrobial activities against human, animal and plant pathogens as protoens as antinociceptive, anti-inflammatory, and extensive antipyretic activity [ 1415 ]. In addition, Wu et al. More than species of mangrove endophytic fungi were isolated and natural products from them showed potential anti-microbial and anti-tumor activity [ 13 ].
Meanwhile, over actinomycetes were isolated from mangroves and their secondary metabolites showed anti-infection, anti-tumor and protein tyrosine phosphatase 1B PTP1B inhibitory activity [ 11 ].
Actinomycetes mangrovee known to be active and numerous components of marine microbial communities as well as diverse in various marine ecosystems including mangroves. This valuable microbial community produces different types of fascinating and structurally complex natural products with biological activity. Numerous researches have indicated that actinomycetes secondary metabolites have potential as new antibiotics, antitumor agents, immunosuppressive agents and enzyme inhibitors [ 17 ].
Up till now, about 23, bioactive compounds produced by microorganisms have been actinomyctes and more than 10, among these compounds were isolated from actinomycetes [ 18 ]. Recently, bioactivity studies of secondary metabolites from mangrove actinomycetes have become a hot spot. The reported screening tests are not only on antimicrobial, antineoplastic and PTP1B inhibitory activity [ 11 ] but also on protease, cellulase, amylase, esterase, l -asparaginase production [ 2021 ].
Compounds with unique structure and potential medicinal use have been obtained from mangrove actinomycetes in recent years. The well-known compound salinosporamide A, is the first and most advanced marine actinomycete secondary metabolite to be processed for clinical trials for cancer treatment, and was actually produced by the Salinispora strain isolated from protlens mangrove sample [ 22 ]. Other examples are the xiamycins, which are indolosesquiterpenes compounds, isolated from prokaryotes for the first time [ 23 ].
Novel indolocarbazoles identified from a mangrove streptomycete present unprecedented cyclic N -glycosidic linkages between 1,3-carbon atoms of the glycosyl moiety and two indole nitrogen atoms of the indolocarbazole core with anticancer activity [ 24 ]. The mangrove environment is a virtually untapped source of novel and diverse natural products and needs much more attention.
The mangrove environment such as geographical location, pH, temperature, salinity, moisture and nutrient differs greatly in prltiens regions so that mangrove actinomycetes are diverse and unique [ 6 ].
So far, 24 genera of 11 families and eight suborders under the actinomycetale containing three new genera have been isolated and identified from mangrove. Streptomyces has the biggest advantage in the ability to produce bioactive compounds as well as isolation quantity [ 25 ]. However, it is difficult to define an individual species or genus as unique mangrove actinomycetes based on the evidence provided by detailed phylogenetic characterization of the actinomycete genus Salinispora that an individual species can be cosmopolitan in distribution when its growth requirements are met [ 26 ].
The limitation of studied bacterial populations and resolution of analytical techniques make it uncertain of detecting bacterial endemism. Even so, new species and genus in mangrove represent to a certain degree the uniqueness of mangrove actinomycetes and indeed produce novel bioactive compounds or chemical scaffolds. In this review, we summarize the vast majority of studies about mangrove actinomycetes natural products and pharmacological activity and attempt to uncover the value of mangrove actinomycetes as an important source of novel and bioactive compounds which could become new and effective marine drugs.
Mangrove rare actinobacteria: taxonomy, natural compound, and discovery of bioactivity
A novel nitrogenous cyclic dipeptide 1 was isolated from the broth of Streptomyces sp. The corresponding chemical structure is shown in Figure 1. Xiamycin 2 and its methyl ester 4 were discovered by Ding et al. These actinommycetes compounds were isolated from prokaryotes for the first time. Xiamycin showed selective anti-HIV activity which specifically blocked R5 tropic HIV-1 infection and its methyl ester was more active in antimicrobial, cytotoxic and antiviral biological assays.
This research group then isolated another three novel ;rotiens, xiamycin B 3indosespene 5sespenine 6 and the known xiamycin A 2 from the culture broth of Streptomyces sp. These three new compounds have been proved to have strong antimicrobial activities against several bacteria, including methicillin-resistant Staphylococcus aureus and protieens Enterococcus faecalis. The same research group continued to unveil the molecular basis for the first indole terpenoid pathway in a bacterium and found two indispensable cyclases including XiaE and XiaF.
The xia biosynthesis enzymes were believed to be a novel addition to the family of terpene synthases and modifying enzymes in bacteria [ 29 ]. In addition, Li et al. SCSIOand identified portiens characterized its gene cluster which revealed an oxidative cyclization strategy tailoring indolosesquiterpene biosynthesis.
What is more, XiaM was identified as an enzyme capable of converting a methyl group to a carboxyl group via triple hydroxylations in xiamycin A biosynthesis [ 31 ]. Streptocarbazoles, novel staurosporine actinomgcetes with unprecedented cyclic N -glycosidic linkages between 1,3-carbon atoms of the glycosyl moiety and two indole nitrogen atoms of the indolocarbazole core were other promising compounds isolated from mangrove actinomycetes.
Streptocarbazoles A 7 and B 8 were obtained from Streptomyces sp. Recently, the first cloning and characterization of an indolocarbazole gene cluster isolated from Streptomyces sanyensis FMA was reported and indolocarbazole biosynthesis was confirmed by gene inactivation and heterologous expression in Streptomyces coelicolor M [ 32 ]. The corresponding chemical structures are shown in Figure 2. A novel alkaloid benzo[f][ 17 ] naphthyridine 10 was isolated from Streptomyces albogriseolus MGR originating from mangrove sediments collected in the national mangrove reserve in Fujian Province of China [ 34 ].
Further study was done protienss Tian et al. The corresponding chemical structure is showed in Figure 3. A new pyrazine derivative compound 11 was isolated from Jishengella endophytica [ 36 ], an endophytic actinomycetes which is a new genus of the Micromonosporaceae family [ 37 ].
This producer strain was isolated from a mangrove plant Acanthus illicifolius root in Hainan, China and compound 11 was proved to have no antivirus effects on H1N1. The corresponding chemical structure is shown in Figure 4. These compounds showed varying degrees of anticancer activities but no activity against Staphylococcus aureus methicillin-resistantEnterococcus faecium vancomycin-resistantand Candida albicans wild-type and amphotericin-resistant and Herpes simplex virus.
Then Liu et al. In addition total synthesis of salinosporamide A was reported by Endo and Danishefsky [ 40 ]. In Potts and Lam [ 41 ] carried out a review about the maangrove and activities of potiens class of compounds from fermentation and natural product chemistry, precursor-directed biosynthesis, mutasynthesis, semi-synthesis, and total synthesis.
Then Potts et al. The clinical trial of Marizomib in melanoma, pancreatic and lung cancer combined with the HDI histone deacetylase inhibitor Vorinostat showed highly synergistic antitumor activities [ 43 ].
Phase I trials in patients with advanced hematologic and solid malignancies also showed rapid, broad and effective proteasome inhibition with no significant PN, neutropenia or thrombocytopenia [ 44 ]. The corresponding chemical structures are shown in Figure 5. K isolated from Ghanaian mangrove river sediment in Butre, Ghana [ 46 ]. The corresponding chemical structures are shown in Figure 6. Inthree new p -aminoacetophenonic acids 22 — 24 were isolated from Streptomyces griseus HKI as an endophyte of the mangrove plant Kandelia candel near Manggrove City of Fujian Province, China.
There was no activity research on these three compounds [ 47 ].
Then another four novel p -aminoacetophenonic acids 25 — 28 were reported in another endophyte Streptomyces sp. The corresponding chemical structures are shown in Figure 7. The structures of p -aminoacetophenonic acids 22 — One new benzamide 29 was produced by a mangrove actinomycete Streptomyces sp. Compound 29 showed no significant Caspase-3 inhibitory activity.
Proriens corresponding chemical structure is shown in Figure 8. An anti-fibrotic benzopyran compound 30 was produced by Streptomyces xiamenensis isolated from a mangrove sediment sample collected in the national mangrove reserve in Fujian Province of China. Xctinomycetes corresponding chemical structure is shown in Figure 9.
JBIR 32 was isolated from Streptomyces sp. RL23 and Actimomycetes collected from mangrove soil in Orotiens with antioxidative activity and it showed 1,1-diphenylpicrylhydrazyl radical scavenging activity with the IC 50 value of The corresponding chemical structures are shown in Figure A novel nitrogenous compound named as p -tolylaminopropanoate 33 was produced by Streptomyces sp.
The corresponding chemical structure is shown in Figure GT collected from the leaves of the mangrove plant Aegiceras comiculatum in Xiamen, Fujian, China. However, these compounds showed no antimicrobial and antiviral activities. It is worth noting that the rare derivatives of compound 35 were isolated from a fungi previously but this is the first time the same type of novel compounds have been rpotiens from an actinomycete.
The mmangrove of cyclopentenone derivatives 34 — A series of nine-membered dilactone antimycins isolated from mangrove actinomycetes also were reported. Antimycin A18 38 with a higher activity against plant pathogenic fungi than blasticidin S a commercialized fungicide was isolated from an endophytic Streptomyces albidoflavus I07A which was isolated from the leaf of B.
Compound 38 was regarded proitens the first natural antimycin which has an 8- O -acetyl side chain. The producer Streptomyces actinomgcetes XM52 was isolated from the rhizosphere of the mangrove plant Avicennia mariana from Fujian Province, China.
Antimycin B1 39 was inactive against the bacteria Bacillus subtilisStaphyloccocus aureus and Loktanella hongkongensisbut antimycin B2 40 showed antibacterial activities against S. A novel dilactone 43 was obtained from an actinomycete strain N in the bottom mud of the Zhanjiang mangrove. This compound was proved to be cytotoxic against human chronic granulocytic leukemia cell line K in vitro with an IC 50 value of 1. HKI of the mangrove tree Bruguiera gymnorrhiza in China.
[Actinomycetes from mangrove and their secondary metabolites]. – Abstract – Europe PMC
Concerning their biological activities, divergolide A 44 showed the strongest activity against Mycobacterium vaccaewhereas divergolide D 47 was more active against Bacillus subtilis and Staphylococcus aureus and displayed prominent activity to lung cancer LXFA Lactinomycdtes cancer PANC-1renal cancer RXF Lmangroce sarcoma Saos-2 with IC 50 values ranging from 1.
Then in Rasapalli et al. A new compound butremycin 48 was isolated from Micromonospora sp. K, the same strain as above and showed weak inhibitory activity against S. A new macrocyclic dilactone 49 named as JBIR with potential anti-MPM malignant pleural mesothelioma activity was obtained from Promicromonospora sp.