Streptomyces sp. MUM273b: A mangrove‐derived potential source for antioxidant and UVB radiation protectants

Abstract Microbial natural products serve as a good source for antioxidants. The mangrove‐derived Streptomyces bacteria have been evidenced to produce antioxidative compounds. This study reports the isolation of Streptomyces sp. MUM273b from mangrove soil that may serve as a promising source of antioxidants and UV‐protective agents. Identification and characterization methods determine that strain MUM273b belongs to the genus Streptomyces. The MUM273b extract exhibits antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging activities and also metal‐chelating activity. The MUM273b extract was also shown to inhibit the production of malondialdehyde in metal‐induced lipid peroxidation. Strong correlation between the antioxidant activities and the total phenolic content of MUM273b extract was shown. In addition, MUM273b extract exhibited cytoprotective effect on the UVB‐induced cell death in HaCaT keratinocytes. Gas chromatography–mass spectrometry analysis detected phenolics, pyrrole, pyrazine, ester, and cyclic dipeptides in MUM273b extract. In summary, Streptomyces MUM273b extract portrays an exciting avenue for future antioxidative drugs and cosmeceuticals development.


| INTRODUC TI ON
Natural products refer to chemical compounds produced by living organisms, for instance, plants, animals, and microorganisms that benefit the producer (Katz & Baltz, 2016). Both terrestrial plants and microorganisms portray indispensable sources for bioactive natural products in drug discovery efforts particularly owing to their exceptionally capability in producing a great number of structurally diverse compounds (Cragg & Newman, 2001;Ma et al., 2018;Tang et al., 2016). The natural products that exhibit pharmacological properties have been harnessed as clinically important drugs to treat diseases. Besides their direct therapeutic use, the fascinating molecular frameworks of natural products offer a range of diverse unique chemotypes as inspiration for the development of current clinically significant drugs or potential novel drugs Nielsen, 2002;Rodrigues, Reker, Schneider, & Schneider, 2016;Tan, Low, et al., 2019). Whereas the natural environment is regarded as a rich source of unique chemical diversity, the reduced trend in the discovery of new bioactive compounds as well as the frequent rediscovery of previously identified compounds have been an increasing challenge for the field of drug discovery from natural products (Lam, 2007;Li & Vederas, 2009). Despite that, many has turned their focus toward natural products derived from difficultto-reach sources/habitats to increase the opportunities for finding novel chemical entities (Desbois, 2014;Xu, 2015).
As of today, estimated 50%-70% of all agents in clinical use are of natural product origin, majority of which are derived from bacteria, particularly the family Actinomycetaceae (Bérdy, 2012).
Ever since the discovery of penicillin and followed by streptomycin as a result of systematic screening of soil actinomycetes by the Waksman (Schatz, Bugle, & Waksman, 1944), microorganisms have been exploited by humans for thousands of years as the biofactories to produce beneficial products for human (Katz & Baltz, 2016;Kemung et al., 2018). Microbes live in every kind of ecological niche, for example, in sediments, thermal vents, and also in extreme environments that are otherwise detrimental to most living organisms on earth (Ghosh, 2012). Previously, terrestrial microbes were known to be rich source of biologically active secondary metabolites with significant pharmaceutical or agrochemical applications. The discovery of various unique bioactive natural products from terrestrial-derived microbes includes the antibiotics: penicillin, streptomycin, vancomycin; antitumor drugs: actinomycin and mitomycin; antiparasitic drug: avermectin, and immunosuppressant drug cyclosporin (Katz & Baltz, 2016). Given the issues of frequent rediscovery of previously identified compounds, many has paid great attention to microbes derived from unique or unusual ecological niches, including the mangrove ecosystem (Xu, 2015).
Mangroves are among the most-prolific and biologically imperative ecosystems on earth, because they bring benefits to human society serving as important sources of food, medicines, fuel, and building materials (Walters et al., 2008) in addition to acting as natural barrier that protects shorelines from devastating natural forces (Alongi, 2008;Quarto, 2005). Besides, mangrove environments harbor high level of microbial diversity such as bacteria, fungi, cyanobacteria, microalgae, macroalgae, and protozoa. Great interest has been given to the exploitation of mangrove-derived microbial natural products owing to their wide variety of bioactivities, which contribute immensely in the industrial and clinical applications (Demain & Sanchez, 2009;Gupta, Gigras, Mohapatra, Goswami, & Chauhan, 2003;. Particularly, the Streptomyces species as the largest genus of Actinobacteria, which has contributed enormously to mankind, has become a prolific producer for bioactive compounds with various bioactivities such as antioxidant, antimicrobial, antitumor, immunosuppressant, and neutroprotective properties (Dan & Sanawar, 2017;Kim et al., 2011;Law, Ser, Duangjai, et al., 2017;Ser et al., 2017;. Together with the numerous discovery of novel Streptomyces species with bioactive potentials recently such as S. malaysiense , S. antioxidans (Ser, Tan, et al., 2016), S. humi (Zainal et al., 2016), S. colonosanans , S. euryhalinus (Biswas, Choudhury, Mahansaria, Saha, & Mukherjee, 2017) from mangrove soil, mangrove-derived Streptomyces represent irreplaceable resources in bioprospecting of natural products with potentially novel chemotypes and promising pharmacological properties.
UV radiation from sunlight has been known to induce harmful responses, including erythema, sunburn, and skin cancer (Brash et al., 1991). Among the three types of solar UV rays, UVB radiation can cause serious skin damage via DNA damage and/or production of reactive oxygen species (ROS) (Nishigori, Hattori, & Toyokuni, 2004). Antioxidants have been shown to exhibit protective effects against UV-induced oxidative damage on skin cells (Salucci et al., sp. MUM273b from Kuala Selangor mangrove soil, Malaysia. The antioxidant and protective potentials of Streptomyces sp. MUM273b extract against UVB-induced cytotoxicity were evaluated. These findings were also well supported with the detection of potential antioxidative compounds by gas chromatography and mass spectrometry analysis. Taken together, this study has further instilled the notion that mangrove Streptomyces serves as a rich source of antioxidants which could greatly benefit future research to cope with oxidative damage induced by UV radiation on skin cells.

| Environmental sampling and strain MUM273b isolation
Mangrove soil samples were collected from Kuala Selangor, Malaysia. Specifically, the site of collection was denoted as MUM-KS1 located at the coordinate (3° 21′ 45.8″ N 101° 18′ 4.5″ E). Prior to the soil sample collection, approximately 3 centimeter of top layer soil was removed. The soil sample was collected from the layer of 20-centimeter depth and kept at −20°C before further processing. During the sample processing, the soil was air-dried and finely grounded before subjected to wet heat pretreatment (15 min at 50°C) (Takahashi, Matsumoto, Seino, Iwai, & Omura, 1996). Serial dilution of the treated soil sample was performed with sterile water to 10-4. Diluted soil suspension was spread onto isolation medium International Streptomyces Project (ISP) 2 (Shirling & Gottlieb, 1966) which was added with cycloheximide (25 µg/ml) and nystatin (10 µg/ ml). A 14 days incubation at 28°C was performed for the inoculated ISP2 agar plate. Pure colony of strain MUM273b was picked and purified with new ISP2 agar. Strain MUM273b was maintained on slants of ISP2 agar at room temperature for short-term storage while in 20% (v/v) glycerol suspensions at −20°C for long-term storage.

| Identification of strain MUM273b by 16S rRNA phylogenetic analysis
Genomic DNA of strain MUM273b was extracted and followed by 16S rRNA gene PCR amplification (Hong et al., 2009). The PCR amplification was conducted as described in Lee, Zainal, Azman, Eng, Ab Mutalib, et al. (2014), Lee, Zainal, Azman, Eng, Goh, et al. (2014) using the primer 27F (5′-GTTTGATCCTGGCTCAG-3′), 1492R (5′-TACGGCTACCTTGTTACGACTT-3′). The 16S rRNA gene of strain MUM273b was sequenced prior to alignment using the CLUSTAL-X software. The representative gene sequences of related type strains of the genus Streptomyces were retrieved from the Genbank database F I G U R E 1 Neighbor-joining phylogenetic tree based on the almost complete 16S rRNA sequences that shows the evolutionary relationships between the strain MUM273b (1406 bp) and representatives of some other related taxa. Bootstrap values (>50%) based on 1,000 re-sampled datasets are shown at branch nodes. Bar, 0.005 substitutions per site (Thompson, Gibson, Plewniak, Jeanmougin, & Higgins, 1997). The alignments were checked and adjusted manually before proceeding to phylogenetic tree construction. The phylogenetic tree of strain MUM273b ( Figure 1) was constructed with the neighbor-joining algorithm (Saitou & Nei, 1987) using MEGA version 6.0 (Tamura, Stecher, Peterson, Filipski, & Kumar, 2013). Kimura's two-parameter model was used to compute the evolutionary distances for the neighbor-joining algorithm (Kimura, 1980). The sequence similarities were calculated based on EzTaxon-e server (http://www.ezbio cloud.net/) (Kim et al., 2012). The bootstrapping based on 1,000 resampling method of Felsenstein (1985) was used to evaluate the stability of the resultant trees topologies.

| Preparation of MUM273b extract
The fermentation process was conducted by inoculating a 14 days broth culture of strain MUM273b into an Erlenmeyer flask containing the Han's Fermentation Media 1 (Biomerge, Malaysia) (Hong et al., 2009;Lee et al., 2012). The inoculated media were fermented in rotary shaker at 200 rpm for 10 days at 28°C. The biomass was separated from the supernatant by centrifugation at 12,000×g for 15 min. The supernatant was filtered using filter paper (Whatman, UK) and freezedried. The dried product was subject to methanol extraction for 72 hr.
Subsequently, the organic solvent was collected by filtration prior to rotary evaporation at 40°C. After total removal of the organic solvent, the product was weighed and dissolved in dimethyl sulfoxide (DMSO).

| Antioxidant activities of MUM273b extract
2.5.1 | DPPH-radical scavenging activity DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity of MUM273b extract was assessed as described in (Ser, Palanisamy, et al., 2015). MUM273b extract was reacted with 0.016% (w/v) DPPH in 95% (v/v) ethanol. For 20 min, the reaction was incubated in the dark at room temperature. The absorbance of the mixture was taken immediately at 515 nm with microplate reader. Gallic acid was the positive control. The following formula was used to calculate the DPPH radical scavenging activity of MUM273b extract:

| ABTS radical scavenging activity
The 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay was performed as described in . ABTS radical cation (ABTS · ) was generated by reacting ABTS stock solution at 7 mM with potassium persulfate at 2.45 mM for 24 hr. The ABTS radical solution was mixed with MUM273b extract preloaded in the 96-well microplate at different concentrations. After 20 min incubation in the dark, the absorbance of the mixture was taken immediately at 734 nm with microplate reader. Gallic acid was the positive control. The following formula was used to compute the percentage ABTS scavenging activity of MUM273b extract:

| Superoxide anion radical scavenging activity
The superoxide anion scavenging activity or superoxide dismutase (SOD)-like activity of MUM273b extract was investigated following the manufacturer's protocol (19160 SOD Assay Kit-WST, Sigma Aldrich).
Briefly, MUM273b extract was mixed with respective reaction solutions accordingly before incubation at 37°C for 30 min. Absorbance of each reaction mixture was measured at 450nm using a microplate reader colorimetrically. The following formula was used to determine the superox-

| Metal chelating activity
Metal chelating activity of MUM273b extract was measured as shown in previous studies (Adjimani & Asare, 2015;Dinis, Madeira, & Almeida, 1994). Briefly, FeSO4 at 2 mM was mixed with serially diluted MUM273b extract. Subsequently, ferrozine (5 mM) was added to start the reaction. After 10 min, absorbances of the mixtures were measured at wavelength of 562 nm. EDTA was the positive control.
The following formula was used to calculate the metal chelating activity of MUM273b extract:

| Lipid peroxidation assay
To assess the inhibitory potential of MUM273b extract against lipid peroxidation, thiobarbituric acid reactive species (TBARS) assay was used to measure the malondialdehyde (MDA) formed from iron-induced lipid peroxidation in lipid-rich media, as described in Dasgupta and De (2004). In short, MUM273b extract was added into the egg homogenate prepared in phosphate-buffered saline (PBS) (10% v/v).
To induce lipid peroxidation, 100 μM of FeSO4 was added to the mixture. After 1 hr, ice-cold 20% trichloroacetic acid was added to stop the reaction in 1 to 1 proportion. The MDA content in the supernatant was obtained by centrifugation at 1,200×g for 10 min and measured by using TBARS assay . The fluorescence intensity of the product was measured by fluorometer at 535 excitation/553nm emission. The following formula was used to calculate the inhibitory effect of MUM273b extract against lipid peroxidation (%): RFI: relative fluorescence intensity; Blank: no extract added.
Absorbance of the mixture in each well was measured at 750 nm.

| UVB irradiation
HaCaT human keratinocytes were seeded in 96-well culture plates at density of 1x10 4 cells/well and incubated in an atmosphere of 5% CO 2 at 37°C overnight for attachment. Prior to UVB irradiation, culture medium was replaced with a thin layer of PBS in the presence or absence of MUM273b extract in a series of concentrations.
The cells were irradiated with Philip UVB Broadband TL 20W/12 phototherapy lamp (Philip, Amsterdam) with a wavelength range between 290 and 315 nm. The intensity of irradiation was 50 mJ/ cm 2 (Mahendra et al., 2019). UV intensity was measured using a UV light meter UV-340A (Lutron, USA). After UVB irradiation, the PBS was replaced with fresh growth medium and incubated in 5% CO 2 at 37°C for 24 hr before subjected to MTT viability assay.

| MTT viability assay
The viability of HaCaT human keratinocytes in the 96-well plate was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Goh & Kadir, 2011). The assay was performed by adding 20 µl of MTT solution (5mg/ml) to each well and incubated at 37°C with 5% CO 2 for 4 hr. The medium was discarded by gentle aspiration. The formazan crystals were dissolved in 100 µl of DMSO and the absorbance of each well was measured spectrophotometrically at 570 nm (with 650 nm as reference wavelength).

| Phase-contrast microscopy
The effect of UVB radiation and the UVB-protective effect of MUM273b extract on HaCaT human keratinocytes were examined morphologically with an inverted light microscope.

| Statistical analysis
All the antioxidant tests were conducted in quadruplicates. Statistical analysis was performed using SPSS software. The significant % Metal chelating activity difference between the treated and untreated groups was determined by one-way analysis of variance (ANOVA) and Tukey's post hoc analysis. A difference was considered statistically significant when p ≤ 0.05. The relationship between the total phenolic content and the antioxidant capacity of the extract was evaluated using Pearson's correlation analysis.  Figure 1).

| Phenotypic characteristics of strain MUM273b
Strain MUM273b is Gram-positive and aerobic.

| Antioxidant activities
Several antioxidant activity assays were performed to assess the possible different mechanisms of MUM273b extract in exerting antioxidant activities.   Table 3). The positive correlation suggested that phenolic compounds may be the main contributor to the radical scavenging activities exhibited by MUM273b extract.

| Inhibition of UVB-induced keratinocyte death
To

| Detection of bioactive compounds in MUM273b extract
The results of GC-MS analysis revealed that MUM273b extract contains several groups of chemical compounds, including the pyrrole, pyrazine, ester, phenols, and cyclic dipeptides. The potential bioactive compounds present in MUM273b extract were identified by referring to the comparison between their mass spectra to standard mass spectra available in the database (W9N11 MS library). Table 4 lists the chemical compounds detected in term of their retention time, molecular weight, and molecular formula. Figure 5 depicts the chemical structures detected in MUM273b extract.

| D ISCUSS I ON
The continuous need for research on natural products is required to keep pace with ever-growing demands for better therapeutics.
Mangrove-associated microbes continue to be the highlight for F I G U R E 3 Effect of MUM273b extract against lipid peroxidation induced by Fe 2+ . MDA level was quantified using TBARS assay. All data are presented as mean ± SD (n = 3). *indicates p < 0.05 between control (without extract) and MUM273b extract added samples. MDA, malondialdehyde; TBARS, thiobarbituric acid reactive species natural product research. Microorganisms that inhabit within the intertidal region are believed to have adapted specific metabolic pathways that aid in resisting the natural stressors such as constant changes of tidal gradient, temperature, and high salinity (McKee, 1995;Xu, 2015) for survival, subsequently leading to synthesis of unique and interesting secondary metabolites (Hong et al., 2009).
Therefore, mangrove environment is becoming the focus of considerable microbiological interest, especially in the effort to discover novel microbial natural product.
Given the growing number of novel bacteria discoveries from mangrove ecosystem, increasing attention has also been placed on the exploration of novel or unusual biomolecules from the mangrove-associated microbes (Xu, 2015). As one of the largest microbial community in the mangrove ecosystem, Streptomyces sp. is known to be valuable and rich bioresources for bioactive compounds, to which numerous have been approved as clinically used drugs (Patridge, Gareiss, Kinch, & Hoyer, 2016;Vilhena & Bettencourt, 2012 (Hong et al., 2009;Lee, Zainal, Azman, Eng, Ab Mutalib, et al., 2014;Lee, Zainal, Azman, Eng, Goh, et al., 2014;Tan et al., 2018). To overcome these environmental stressors, these microbes are required to produce unique metabolites for their survival (Hong et al., 2009

F I G U R E 4 Protective effect of MUM273b extract against UVB-induced cytotoxicity in HaCaT keratinocytes. (a)
The HaCaT cells were exposed to UVB (50 mJ/cm 2 ) in the presence of MUM273b extract at different concentrations. The cell viability was measured by MTT assay after 24 hr. All data are present as mean ± SD (n = 5). # indicates p < 0.05 between control (without UVB) and cells exposed to UVB (50 mJ/cm 2 ). *indicates p < 0.05 between cells (without extract) and MUM273b extract-treated cells after UVB exposure. (b) The morphological changes of HaCaT cells observed under phase-contrast microscopy (×100) biosynthesis of valuable secondary metabolites, thereby it was found to cluster with S. albogriseolus and S. viridodiastaticus which were previously reported to produce numerous bioactive metabolites (Li, Xu, Zhao, & Xu, 2010;Singh et al., 1994). To have a better understanding of the strain, we also performed phenotypic characterization of strain MUM273b including its morphological, physiological, and biochemical properties. The color of aerial mycelium is yellow and the substrate mycelium is pale-yellow. Strain MUM273b was found to be capable of digesting both starch and CMC, suggesting that strain MUM273b may have the potential to be employed as industrial important strain for the production of essential enzymes such as amylase and cellulase. Furthermore, strain MUM273b demonstrates high salinity tolerance to 8% (w/v) NaCl and moderate temperature tolerance up to 40°C, as these characteristics are crucial to be equipped by mangrove-associated microbes for their survival in the dynamic mangrove ecosystem.
The composition of substrates available during growth has great impact on the secondary metabolism of Streptomyces sp. (Ser, Law, et al., 2016). Thus, Biolog GEN III MicroPlate system was utilized to determine metabolic profile of strain MUM273b by determining the types of carbon and nitrogen utilization. The utilization assay showed that strain MUM273b was able to utilize a range of carbon and nitrogen sources, such as monosaccharides (α-d-glucose, d-fructose, d-galactose); disaccharides (d-maltose, α-d-lactose, d-trehalose but not sucrose); polysaccharides (pectin, gelatin and dextrin); glycoside (N-acetyl-d-glucosamine), amino acids (l-arginine, l-histidine and l-serine), and sugar alcohols (d-mannitol and d-sorbitol). Having these data, the process of medium optimization could be aided in future to improve the synthesis of desirable bioactive compounds at a larger scale.
Human skin cells or keratinocytes, as the major targets of UV, are constantly under oxidative stress induced by UVB irradiation via ROS generation, subsequently leading to cell death (Brash et al., 1991;Portugal, Barak, Ginsburg, & Kohen, 2007). Given that the ROS play pivotal roles in cell-damaging oxidation process, cell or an organism's defense against of oxidative stress or attack by ROS could be prevented by antioxidants. Antioxidants function to protect cell or an organism from oxidative stress through neutralization of ROS which induces oxidative damages (Apak, Özyürek, Güçlü, & Çapanoğlu, 2016;Halliwell, 2011). The antioxidants function in several ways such as scavenging free radicals, interfering autoxidation chain reaction, converting the ROS into stable compounds, and chelating metal prooxidants (Devasagayam et al., 2004;Lobo, Patil, Phatak, & Chandra, 2010). The reason for being that the total antioxidant capacity of MUM273b extract was examined by several in vitro antioxidant assays. DPPH and ABTS assays are based on single electron transfer reaction (Prieto, Curran, Gowen, & Vázquez, 2015).
This type of antioxidant assay evaluates the ability of a substance/ extract to neutralize the radical indicators through different mechanisms such as electron transfer or hydrogen transfer. Generally, these rapid and simple assays serve as preliminary screening to assess the antioxidant potential of the extract. Given that the DPPH and ABTS radicals are not present in the biological systems, MUM273b extract was further tested for superoxide anion scavenging activity. The ability of MUM273b extract to scavenge O 2 ·− suggested that it may lower the O 2 ·− level as high O 2 ·− level has been associated to many pathological conditions such as cancer and cardiovascular diseases (Fukai, Folz, Landmesser, & Harrison, 2002;Lopez-Lazaro, 2007;Pervaiz & Clement, 2007). Moreover, O 2 ·− is also the precursor of numerous reactive oxygen intermediates, including the highly reactive peroxynitrite molecule (ONOO -) and hydroxide radical ( · OH) (Bergamini et al., 2004). Therefore, the control of O 2 ·− generation is of great important with the aim to maintain the balance between the production rate of O 2 ·− and antioxidant capacity of the endogenous SOD enzymes defense system to protect from oxidative damages.
Iron is essential for all forms of life. However, excess iron can catalyze the Fenton reaction which involves the decomposition of hydrogen peroxide, leading to generation of ROS which damages lipids, proteins, and DNA (Prousek, 2007). Cutaneous damage has also been associated to iron-catalyzed ROS generation (Kitazawa, Iwasaki, & Sakamoto, 2006). Thus, the ability of MUM273b extract in chelating metal is promising as it may reduce the increased catalytic iron level in skin resulted from the release of iron from ferritin upon exposure to UV radiation (Kitazawa et al., 2006). Furthermore, lipid peroxidation occurs when ROS damage cell membrane by peroxidation of fatty acids within the phospholipid membrane. The increased iron content in response to UV radiation could further accelerate lipid peroxidation, resulting in the production of mutagenic substances such as MDA (Halliwell & Chirico, 1993;Hazra, Biswas, & Mandal, 2008). This study demonstrated that MUM273b extract reported Streptomyces extracts, in term of their radical scavenging and metal chelating activities  ABTS radical scavenging activity with 12.33 ± 3.07% at 2 mg/ml (Law et al., 2019). Nevertheless, this study shows that MUM273b extract was capable of attenuating the UVB-induced cytotoxicity in HaCaT cells and serves as the first report of Streptomyces strain isolated from Malaysia mangrove soil exhibiting UVB-protective activity. Taken together, these findings suggested that the cytoprotective effect of MUM273b extract against UVB irradiation might be due to its antioxidant properties, including scavenging free radicals and inhibiting lipid peroxidation.
Phenolic compounds have been well recognized for their antioxidant properties (Martins, Barros, & Ferreira, 2016;Shahidi & Ambigaipalan, 2015). The strong correlation between the tested antioxidant capacity and the total phenolic content suggested the presence of phenolic compounds in MUM273b extract and attributed to its antioxidant properties. Phenolic antioxidants have been known to interfere with oxidation process, mediating through free radical terminators and also metal chelators (Zamora & Hidalgo, 2016).
Studies evidenced that phenolic compounds are effective in exerting protective effect against pathological conditions such as cancer and cardiovascular disease (Martins et al., 2016 (Tan, Ser, et al., 2015).
Therefore, the antioxidant capacity of MUM273b extract could be conferred by the phenolic compounds.

| CON CLUS ION
In summary, the research work isolated a Streptomyces strain derived from mangrove soil in Malaysia, which exhibits antioxidants producing abilities. The extract of the fermented broth of Streptomyces strain MUM273b exhibits DPPH, ABTS, and superoxide anion radicals scavenging activities. MUM273b extract was also capable of chelating metal ion and inhibiting iron-induced lipid peroxidation.
MUM273b extract also protected keratinocytes against UVB-induced cytotoxicity. The presence of bioactive constituents including phenolic compounds and cyclic dipeptides may be responsible for the antioxidant and UVB-protective activities of MUM273b extract. As a whole, the results of this study highlighted that the mangrove-derived Streptomyces in particular strain MUM273b possess immense potential to synthesize antioxidative and UVBprotective metabolites and hence could be exploited for future development as a functional ingredient in cosmeceutical applications. 02-02-10-SF0215).

CO N FLI C T O F I NTE R E S T S
The authors declare no conflict of interest.

E TH I C S S TATEM ENT
None required.

DATA ACCE SS I B I LIT Y
All data are provided in full in the results section of this paper apart from the 16S rRNA gene sequence of strain MUM273b which is available at www.ncbi.nlm.nih.gov/genba nk/ under accession number MK611768.