Investigation of diverse biosynthetic secondary metabolites gene clusters using genome mining of indigenous Streptomyces strains isolated from saline soils in Iran
-
Amin Khoshakhlagh
,
Seyed Soheil Aghaei
,
Saeid Abroun
,
Mohammad Soleimani
,
Mohammad Reza Zolfaghari
Abstract
Background and Objectives: Bioactive secondary metabolites are the products of microbial communities adapting to environmental challenges, which have yet remained anonymous. As a result of demands in the pharmaceutical, agricultural, and food industries, microbial metabolites should be investigated. The most substantial sources of secondary metabolites are Streptomyces strains and are potential candidates for bioactive compound production. So, we used genome mining and bioinformatics to predict the isolates secondary metabolites, biosynthesis, and potential pharmaceuticals.
Materials and Methods: This is a bioinformatics part of our previous experimental research. Here, we aimed to inspect the underlying secondary metabolite properties of 20 phylogenetically diverse Streptomyces species of saline soil by a rationalized computational workflow by several software tools. We examined the Metabolites' cytotoxicity and antibacterial effects using the MTT assay and plate count technique, respectively.
Results: Among Streptomyces species, three were selected for genome mining and predicted novel secondary metabolites and potential drug abilities. All 11 metabolites were cytotoxic to A549, but ectoine (p≤0.5) and geosmin (p≤0.001) significantly operated as an anti-cancer drug. Metabolites of oxytetracycline and phosphinothricin (p≤0.001), 4Z-annimycin and geosmin (p≤0.01), and ectoine (p≤0.5) revealed significant antibacterial activity.
Conclusion: Of all the 11 compounds investigated, annimycin, geosmin, phosphinothricin, and ectoine had antimicrobial properties, but geosmin also showed very significant anti-cancer properties.
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17. Nga NTH, Ngoc TTB, Trinh NTM, Thuoc TL, Thao DTP. Optimization and application of MTT assay in determining density of suspension cells. Anal Biochem 2020; 610: 113937.
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22. McClure RA, Goering AW, Ju K-S, Baccile JA, Schroeder FC, Metcalf WW, et al. Elucidating the Rimosamide-detoxin natural product families and their biosynthesis using metabolite/gene cluster Correlations. ACS Chem Biol 2016; 11: 3452-3460.
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Microbiol Res 2020; 231: 126374.
24. Nguyen QD,Truong PM,Thanh Vo TNT, Chu TDX, Nguyen CH. Draft genome sequence data of Streptomyces sp. SS1-1, an endophytic strain showing cytotoxicity against the human lung cancer A549 cell line. Data Brief 2020; 30: 105497.
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26. Zhang W, Ames BD, Tsai S-C, Tang Y. Engineered biosynthesis of a novel amidated polyketide, using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase. Appl Environ Microbiol 2006; 72: 2573-2580.
27. Pickens LB, Tang Y. Oxytetracycline biosynthesis. J Biol Chem 2010; 285: 27509-27515.
28. Parkinson EI, Tryon JH, Goering AW, Ju K-S, McClure RA, Kemball JD, et al. Discovery of the tyrobetaine natural products and their biosynthetic gene cluster via Metabologenomics. ACS Chem Biol 2018; 13: 1029-1037.
29. Singh SB, Jayasuriya H, Salituro GM, Zink DL, Shafiee A, Heimbuch B, et al. The complestatins as HIV-1 integrase inhibitors. Efficient isolation, structure elucidation, and inhibitory activities of isocomplestatin, chloropeptin I, new complestatins, A and B, and acid-hydrolysis products of chloropeptin I. J Nat Prod 2001; 64: 874-882.
30. Kalan L, Gessner A, Thaker Maulik N, Waglechner N, Zhu X, Szawiola A, et al. A cryptic polyene biosynthetic gene cluster in Streptomyces calvus is expressed upon complementation with a functional bldA gene. Chem Biol 2013; 20: 1214-1224.
31. Schinko E, Schad K, Eys S, Keller U, Wohlleben W. Phosphinothricin-tripeptide biosynthesis: an original version of bacterial secondary metabolism? Phytochemistry 2009; 70: 1787-1800.
32. Kautsar SA, Blin K, Shaw S, Weber T, Medema MH. BiG-FAM: the biosynthetic gene cluster families database. Nucleic Acids Res 2021; 49: D490-D497.
33. Nguyen HT, Pokhrel AR, Nguyen CT, Pham VTT, Dhakal D, Lim HN, et al. Streptomyces sp. VN1, a producer of diverse metabolites including non-natural furan-type anticancer compound. Sci Rep 2020; 10: 1756.
34. Wittmar J, Meyer S, Sieling T, Kunte J, Smiatek J, Brand I. What does ectoine do to DNA? A molecular-scale picture of compatible solute–biopolymer interactions. J Phys Chem B 2020; 124: 7999-8011.
35. Hützler WM, Mossou E, Vollrath R, Kohagen M, El Ghrissi I, Grininger M, et al. Complex transitions between dihydrate and anhydrate forms of ectoine–unexpected behavior of a highly hygroscopic compatible solute in the solid state. CrystEngComm 2020; 22: 169-172.
2. Law JW-F, Law LN-S, Letchumanan V, Tan LT-H, Wong SH, Chan KG, et al. Anticancer drug discovery from microbial sources: The unique mangrove streptomycetes. Molecules 2020; 25: 5365.
3. Selim MSM, Abdelhamid SA, Mohamed SS. Secondary metabolites and biodiversity of actinomycetes. J Genet Eng Biotechnol 2021; 19: 72.
4. WHO. New report calls for urgent action to avert antimicrobial resistance crisis 2019; Available from: https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis
5. Vasilchenko AS, Julian WT, Lapchinskaya OA, Katrukha GS, Sadykova VS, Rogozhin EA. A novel peptide antibiotic produced by Streptomyces roseoflavus strain INA-Ac-5812 with directed activity against Gram-positive bacteria. Front Microbiol 2020; 11: 556063.
6. Zhong Z, He B, Li J, Li Y-X. Challenges and advances in genome mining of ribosomally synthesized and post-translationally modified peptides (RiPPs). Synth Syst Biotechnol 2020; 5: 155-172.
7. Liu R, Deng Z, Liu T. Streptomyces species: ideal chassis for natural product discovery and overproduction. Metab Eng 2018; 50: 74-84.
8. Crits-Christoph A, Diamond S, Butterfield CN, Thomas BC, Banfield JF. Novel soil bacteria possess diverse genes for secondary metabolite biosynthesis. Nature 2018; 558: 440-444.
9. Albarano L, Esposito R, Ruocco N, Costantini M. Genome mining as new challenge in natural products discovery. Mar Drugs 2020; 18: 199.
10. Lee N, Hwang S, Kim J, Cho S, Palsson B, Cho B-K. Mini review: Genome mining approaches for the identification of secondary metabolite biosynthetic gene clusters in Streptomyces. Comput Struct Biotechnol J 2020; 18: 1548-1556.
11. Jafari S, Aghaei S-S, Afifi-Sabet H, Shams-Ghahfarokhi M, Jahanshiri Z, Gholami-Shabani M, et al. Exploration, antifungal and antiaflatoxigenic activity of halophilic bacteria communities from saline soils of Howze-Soltan playa in Iran. Extremophiles 2018; 22: 87-98.
12. Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman DJ, Ostell J, et al. GenBank. Nucleic Acids Res 2013; 41: D36-42.
13. Liu M, Zhao S, Wang Z, Wang Y, Liu T, Li S, et al. Identification of metabolites of deoxyschizandrin in rats by UPLC-Q-TOF-MS/MS based on multiple mass defect filter data acquisition and multiple data processing techniques. J Chromatogr B Analyt Technol Biomed Life Sci 2014; 949-950: 115-126.
14. Blin K, Shaw S, Kloosterman AM, Charlop-Powers Z, Van Wezel GP, Medema MH, et al. AntiSMASH 6.0: improving cluster detection and comparison capabilities. Nucleic Acids Res 2021; 49: W29-W35.
15. Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res 2021; 49: D1388–D1395.
16. Bateman A, Martin M-J, Orchard S, Magrane M, Agivetova R, Ahmad S, et al. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res 2021; 49: D480-D489.
17. Nga NTH, Ngoc TTB, Trinh NTM, Thuoc TL, Thao DTP. Optimization and application of MTT assay in determining density of suspension cells. Anal Biochem 2020; 610: 113937.
18. Saeedi P, Halabian R, Fooladi AAI. Antimicrobial effects of mesenchymal stem cells primed by modified LPS on bacterial clearance in sepsis. J Cell Physiol 2019; 234: 4970-4986.
19. Dallavecchia DL, Ricardo E, Da Silva AS, Rodrigues AG. Antibacterial and antifungal activity of excretions and secretions of Calliphora vicina. Med Vet Entomol 2021; 35: 225-229.
20. Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Ostell J, Pruitt KD, et al. GenBank. Nucleic Acids Res 2018; 46: D41-D47.
21. Hermann L, Mais C-N, Czech L, Smits SHJ, Bange G, Bremer E. The ups and downs of ectoine: structural enzymology of a major microbial stress protectant and versatile nutrient. Biol Chem 2020; 401: 1443-1468.
22. McClure RA, Goering AW, Ju K-S, Baccile JA, Schroeder FC, Metcalf WW, et al. Elucidating the Rimosamide-detoxin natural product families and their biosynthesis using metabolite/gene cluster Correlations. ACS Chem Biol 2016; 11: 3452-3460.
23. Salwan R, Sharma V. Molecular and biotechnological aspects of secondary metabolites in actinobacteria.
Microbiol Res 2020; 231: 126374.
24. Nguyen QD,Truong PM,Thanh Vo TNT, Chu TDX, Nguyen CH. Draft genome sequence data of Streptomyces sp. SS1-1, an endophytic strain showing cytotoxicity against the human lung cancer A549 cell line. Data Brief 2020; 30: 105497.
25. Cane DE, He X, Kobayashi S, Ōmura S, Ikeda H. Geosmin Biosynthesis in Streptomyces avermitilis. Molecular cloning, expression, and mechanistic study of the Germacradienol/Geosmin synthase. J Antibiot (Tokyo) 2006; 59: 471-479.
26. Zhang W, Ames BD, Tsai S-C, Tang Y. Engineered biosynthesis of a novel amidated polyketide, using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase. Appl Environ Microbiol 2006; 72: 2573-2580.
27. Pickens LB, Tang Y. Oxytetracycline biosynthesis. J Biol Chem 2010; 285: 27509-27515.
28. Parkinson EI, Tryon JH, Goering AW, Ju K-S, McClure RA, Kemball JD, et al. Discovery of the tyrobetaine natural products and their biosynthetic gene cluster via Metabologenomics. ACS Chem Biol 2018; 13: 1029-1037.
29. Singh SB, Jayasuriya H, Salituro GM, Zink DL, Shafiee A, Heimbuch B, et al. The complestatins as HIV-1 integrase inhibitors. Efficient isolation, structure elucidation, and inhibitory activities of isocomplestatin, chloropeptin I, new complestatins, A and B, and acid-hydrolysis products of chloropeptin I. J Nat Prod 2001; 64: 874-882.
30. Kalan L, Gessner A, Thaker Maulik N, Waglechner N, Zhu X, Szawiola A, et al. A cryptic polyene biosynthetic gene cluster in Streptomyces calvus is expressed upon complementation with a functional bldA gene. Chem Biol 2013; 20: 1214-1224.
31. Schinko E, Schad K, Eys S, Keller U, Wohlleben W. Phosphinothricin-tripeptide biosynthesis: an original version of bacterial secondary metabolism? Phytochemistry 2009; 70: 1787-1800.
32. Kautsar SA, Blin K, Shaw S, Weber T, Medema MH. BiG-FAM: the biosynthetic gene cluster families database. Nucleic Acids Res 2021; 49: D490-D497.
33. Nguyen HT, Pokhrel AR, Nguyen CT, Pham VTT, Dhakal D, Lim HN, et al. Streptomyces sp. VN1, a producer of diverse metabolites including non-natural furan-type anticancer compound. Sci Rep 2020; 10: 1756.
34. Wittmar J, Meyer S, Sieling T, Kunte J, Smiatek J, Brand I. What does ectoine do to DNA? A molecular-scale picture of compatible solute–biopolymer interactions. J Phys Chem B 2020; 124: 7999-8011.
35. Hützler WM, Mossou E, Vollrath R, Kohagen M, El Ghrissi I, Grininger M, et al. Complex transitions between dihydrate and anhydrate forms of ectoine–unexpected behavior of a highly hygroscopic compatible solute in the solid state. CrystEngComm 2020; 22: 169-172.
| Files | ||
| Issue | Vol 14 No 6 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v14i6.11263 | |
| Keywords | ||
| Streptomyces; Streptomyces metabolite; Biological products; Bioinformatics | ||
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How to Cite
1.
Khoshakhlagh A, Aghaei SS, Abroun S, Soleimani M, Zolfaghari MR. Investigation of diverse biosynthetic secondary metabolites gene clusters using genome mining of indigenous Streptomyces strains isolated from saline soils in Iran. Iran J Microbiol. 2022;14(6):881-890.
