Exploration of Chemical Diversity and Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular Modelling
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sarcophyton Glaucum Collection
2.2. Chemicals
2.3. Actinomycetes Isolation
2.4. Molecular Identification
2.5. Fermentation and Extraction
2.6. Metabolomic Profiling
2.7. In Vitro Antitrypanosomal Activity
2.8. Statistical and Multivariate Analysis
2.9. In Silico Biological Activity Predictions
2.10. Docking Experiments
2.11. Statistical Analysis
3. Results and Discussion
3.1. Identification and Phylogenetic Analysis of the Isolated Actinomycetes
3.2. In Vitro Antitrypanosomal Activity
3.3. Metabolomic Profiling and Multivariate Analysis
3.4. Bioactivity–Metabolites Correlation
3.5. In Silico Predictions
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Isolate | Accession ID | Identity [%] | Source | Ref |
---|---|---|---|---|
Micromonospora terminaliae DSM 101760 | CP045309.1 | 93.28 | Surface sterilized stem of Thai medicinal plant Terminalia mucronata | [32] |
Micromonospora cremea CR30 | NR_108478.1 | 93.00 | rhizosphere of Pisum sativum | [33] |
Micromonospora palomenae NEAU-CX1 | NR_136848.1 | 92.81 | Nymphs of stinkbug (Palomena viridissima Poda) | [34] |
Micromonospora rosaria DSM 803 | NR_026282.1 | 92.75 | unknown | [35] |
Culture Condition (IC50) * | No. | Retention Time | Mass | Molecular Formula | Dereplication | VIP ** Score |
---|---|---|---|---|---|---|
Streptomyces sp. UR23 on solid media (16.6 ± 1.8) | 1 | 2.81 | 151.0623 | C8H9NO2 | Streptokordin | 2.35 |
2 | 3.44 | 600.3487 | C27H48N6O9 | Nocardamine | 2.22 | |
3 | 8.83 | 560.3537 | C25H48N6O8 | Desferrioxamine B | 2.15 | |
4 | 1.81 | 157.0368 | C6H7NO4 | Clavam-2-carboxylic acid | 1.86 | |
Streptomyces sp. UR23 in liquid media (>100) | 5 | 2.76 | 174.0881 | C8H14O4 | Vertimycin | 2.2 |
6 | 2.06 | 185.0681 | C8H11NO4 | Alaremycin | 1.98 | |
7 | 3.72 | 191.0947 | C11H13NO2 | Streptopyrrolidine | 1.91 | |
8 | 4.1 | 304.1408 | C16H20N2O4 | Tomaymycin | 1.85 | |
9 | 3.21 | 314.1629 | C18H22N2O3 | Streptomycindole | 1.82 | |
Streptomyces sp. UR23 with Nocardia sp. UR27 on solid media (4.6 ± 1.5) | 10 | 7.81 | 604.397 | C35H56O8 | Bafilomycin D | 1.97 |
11 | 7.89 | 622.4075 | C35H58O9 | Bafilomycin A1 | 1.8 | |
12 | 4.57 | 316.2599 | C18H36O4 | Aggreceride A | 1.75 | |
13 | 1.86 | 321.1425 | C13H23NO8 | Salbostatin | 1.73 | |
Streptomyces sp. UR23 with Nocardia sp. UR27 in liquid media (2.4 ± 1.1) | 14 | 11.85 | 491.3616 | C29H49NO5 | Lipstatin | 2.29 |
15 | 4.19 | 287.1518 | C17H21NO3 | Trichostatic acid | 1.87 | |
16 | 4.14 | 302.1626 | C17H22N2O3 | Trichostatin A | 1.77 | |
17 | 3.71 | 346.1522 | C18H22N2O5 | Terreusinol | 1.71 | |
18 | 3.32 | 370.2339 | C20H34O6 | Platenolide II | 1.68 | |
Micromonospora sp. UR17 on solid media (7.8 ± 1.2) | 19 | 5.13 | 598.1115 | C32H22O12 | Crisamicin A | 2.33 |
20 | 3.14 | 158.0934 | C8H14O3 | Mycinonic acid I | 2.11 | |
21 | 2.49 | 168.0414 | C8H8O4 | Vanillic acid | 1.83 | |
22 | 2.13 | 242.0793 | C12H10N4O2 | Lumichrome | 1.66 | |
Micromonospora sp. UR17 in liquid media (>100) | 23 | 3.91 | 352.2236 | C20H32O5 | Neorustmicin D | 2.22 |
24 | 2.55 | 366.1274 | C13H22N2O10 | Trehazolin | 1.95 | |
25 | 3.96 | 366.2106 | C14H30N4O7 | Fortimicin-KK1 | 1.87 | |
Micromonospora sp. UR17 with Nocardia sp. UR27 on solid media (2.7 ± 0.7) | 26 | 3.54 | 304.1205 | C19H16N2O2 | Neihumicin | 1.77 |
27 | 5.89 | 645.3873 | C36H66NO9 | Antascomicin D | 1.71 | |
28 | 5.23 | 689.4139 | C38H59NO10 | Antascomicin C | 1.65 | |
Micromonospora sp. UR17 with Nocardia sp. UR27 in liquid media (2.5 ± 0.9) | 29 | 4.43 | 560.2731 | C29H40N2O9 | Geldanamycin | 1.86 |
30 | 2.22 | 152.0467 | C8H8O3 | 2-Hydroxyphenylacetic acid | 1.82 | |
31 | 3.31 | 254.0573 | C15H10O4 | Daidzein | 1.73 | |
32 | 2.79 | 234.0888 | C13H14O4 | GTRI-02 | 1.66 | |
Nocardiopsis sp. UR17 in solid media (>100) | 33 | 2.29 | 193.0736 | C10H11NO3 | Nocazoline A | 1.84 |
34 | 3.73 | 336.1473 | C20H20N2O3 | Nocazine C | 1.71 | |
Nocardiopsis sp. UR17 on liquid media (>100) | 35 | 4.24 | 369.2418 | C22H31N3O2 | Pendolmycin | 1.64 |
Nocardiopsis sp. UR17 with Nocardia sp. UR27 on solid media (>100) | 36 | 2.64 | 125.0471 | C6H7NO2 | Methyl pyrrole-2-carboxylate | 1.99 |
37 | 3.87 | 139.0272 | C6H5NO3 | 5-hydroxypicolinic acid | 1.85 | |
Nocardiopsis sp. UR17 with Nocardia sp. UR27 in liquid media (>100) | 38 | 2.41 | 195.0524 | C9H9NO4 | Forphenicine | 1.76 |
Nocardia sp. UR27 on solid media (>100) | 39 | 2.66 | 248.1310 | C17H16N2 | Brasilidine A | 2.13 |
40 | 1.72 | 267.0957 | C10H13N5O4 | Formycin-A | 1.92 | |
41 | 2.56 | 282.1204 | C13H18N2O5 | Corynecin III | 1.7 | |
Nocardia sp. UR27 in liquid media (>100) | 42 | 3.86 | 284.0790 | C15H12N2O4 | Deoxynyboquinone | 1.98 |
43 | 3.7 | 366.2039 | C20H30O6 | Spirocardin A | 1.73 | |
44 | 2.92 | 368.2188 | C20H32O6 | Spirocardin B | 1.71 |
NO. | Dereplication | Mass | Molecular Formula | Reported Activity | Probability p < 0.01 |
---|---|---|---|---|---|
3 | Desferrioxamine B | 560.3537 | C25H48N6O8 | Siderophore | 2.42 × 10−6 |
2 | Nocardamine | 600.3487 | C27H48N6O9 | Siderophore | 3.33 × 10−5 |
16 | Trichostatin A | 302.1626 | C17H22N2O3 | Histone deacetylase and tyrosinase inhibitor | 1.22 × 10−5 |
10 | Bafilomycin D | 604.397 | C35H56O8 | Insecticidal activity | 5.43 × 10−4 |
28 | Antascomicin C | 689.4139 | C38H59NO10 | Antimicrobial | 2.66 × 10−4 |
11 | Bafilomycin A1 | 622.4075 | C35H58O9 | H+-ATPase inhibitor | 1.12 × 10−4 |
14 | Lipstatin | 491.3616 | C29H49NO5 | Pancreatic lipase inhibitor | 6.89 × 10−3 |
26 | Neihumicin | 304.1205 | C19H16N2O2 | Cytotoxic | 3.11 × 10−3 |
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Gamaleldin, N.M.; Bakeer, W.; Sayed, A.M.; Shamikh, Y.I.; El-Gendy, A.O.; Hassan, H.M.; Horn, H.; Abdelmohsen, U.R.; Hozzein, W.N. Exploration of Chemical Diversity and Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular Modelling. Antibiotics 2020, 9, 629. https://doi.org/10.3390/antibiotics9090629
Gamaleldin NM, Bakeer W, Sayed AM, Shamikh YI, El-Gendy AO, Hassan HM, Horn H, Abdelmohsen UR, Hozzein WN. Exploration of Chemical Diversity and Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular Modelling. Antibiotics. 2020; 9(9):629. https://doi.org/10.3390/antibiotics9090629
Chicago/Turabian StyleGamaleldin, Noha M., Walid Bakeer, Ahmed M. Sayed, Yara I. Shamikh, Ahmed O. El-Gendy, Hossam M. Hassan, Hannes Horn, Usama Ramadan Abdelmohsen, and Wael N. Hozzein. 2020. "Exploration of Chemical Diversity and Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular Modelling" Antibiotics 9, no. 9: 629. https://doi.org/10.3390/antibiotics9090629