Abstract
In the course of a screening program for bioactive compounds from a marine natural product library, a newly isolated Actinomycetes strain, designated as MS100061, exhibited strong anti-Mycobacterium bovis Bacillus Calmette–Guérin (BCG) activity. The strain belongs to the genus Streptomyces according to its morphological and 16S rDNA phylogenetic analysis. Bioassay-guided isolation resulted in a new spirotetronate, lobophorin G (1), together with two known compounds, lobophorins A (2) and B (3). The structures were elucidated by extensive spectroscopic methods and comparison with literatures. Compounds 1–3 were subjected to anti-BCG, antituberculosis, and antibacterial screening and exhibited potent anti-BCG activity with minimum inhibitory concentration (MIC) values of 1.56, 1.56, and 0.78 μg/ml, respectively, and moderate anti-Mycobacterium tuberculosis H37Rv activity with MIC values of 32, 32, and 16 μg/ml, respectively. The MIC values of compounds 1–3 against Bacillus subtilis were 3.125, 12.5, and 1.56 μg/ml, respectively, indicating great potential for antibacterial drugs. In addition, this is the first report of the anti-BCG and antituberculosis activities of lobophorins.
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References
Ashforth EJ, Fu CZ, Liu XY, Dai HQ, Song FH, Guo H, Zhang LX (2010) Bioprospecting for antituberculosis leads from microbial metabolites. Nat Prod Rep 27:1709–1719
Bernan VS, Greenstein M, Maiese WM (1997) Marine microorganisms as a source of new natural products. Adv Appl Microbiol 43:57–90
Brunk U, Collins VP, Arro E (1981) The fixation, dehydration, drying and coating of cultured cells of SEM. J Microsc 123:121–131
Buchanan GO, Williams PG, Feling RH, Kauffman CA, Jensen PR, Fenical W (2005) Sporolides A and B: structurally unprecedented halogenated macrolides from the marine actinomycete Salinispora tropica. Org Lett 7:2731–2734
Charan RD, Schlingmann G, Janso J, Bernan V, Feng X, Carter GT (2004) Diazepinomicin, a new antimicrobial alkaloid from a marine Micromonospora sp. J Nat Prod 67:1431–1433
Chen CX, Song FH, Wang Q, Abdel-Mageed WM, Guo H, Fu CZ, Hou WY, Dai HQ, Liu XT, Yang N, Xie F, Yu K, Chen RX, Zhang LX (2012) A marine-derived Streptomyces sp. MS449 produces high yield of actinomycin X2 and actinomycin D with potent anti-tuberculosis activity. Apply Microbiol Biotechnol 95:919–927
Cowley SC, Av-Gay Y (2001) Monitoring promoter activity and protein localization in Mycobacterium spp. using green fluorescent protein. Gene 264:225–231
Feling RH, Buchanan GO, Mincer TJ, Kauffman CA, Jensen PR, Fenical W (2003) Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial sources, a marine bacterium of the new genus Salinospora. Angew Chem Int Ed Engl 42:355–357
Fiedler HP, Bruntner C, Bull AT, Ward AC, Goodfellow M, Potterat O, Puder C, Mihm G (2005) Marine actinomycetes as a source of novel secondary metabolites. Atonie van Leeuwenhoek 87:37–42
Igarashi Y, Iida T, Oku N, Watanabe H, Furihata K, Miyanouchi K (2012) Nomimicin, a new spirotetronate-class polyketide from an actinomycete of the genus Actinomadura. J Antibiot 65:355–359
Jensen PR, Mincer TJ, Williams PG, Fenical W (2005) Marine actinomycete diversity and natural product discovery. Antonie van Leeuwenhoek 87:43–48
Jiang ZD, Jensen PR, Fenical W (1999) Lobophorins A and B, new antiinflammatory macrolides produced by a tropical marine bacterium. Bioorg Med Chem Lett 9:2003–2006
Lam KS (2006) Discovery of novel metabolites from marine actinomycetes. Curr Opin Microbiol 9:245–251
Liu XY, Ashforth E, Ren B, Song FH, Dai HQ, Liu M, Wang J, Xie Q, Zhang LX (2010) Bioprospecting microbial natural product libraries from the marine environment for drug discovery. J Antibiot 63:415–422
Liu XT, Chen CX, He WN, Huang P, Liu MM, Wang Q, Guo H, Bolla K, Lu Y, Song FH, Dai HQ, Liu M, Zhang LX (2012a) Exploring anti-TB leads from natural products library originated from marine microbes and medicinal plants. Antonie Van Leeuwenhoek 102:447–461
Liu XT, Schwan WR, Volk TJ, Rott M, Liu MM, Huang P, Liu Z, Wang Y, Zitomer NC, Sleger C, Hartsel S, Monte A, Zhang LX (2012b) Antibacterial spirobisnaphthalenes from the North American cup fungus, Urnula craterium. J Nat Prod 75:1534–1538
Niu S, Li S, Chen Y, Tian X, Zhang H, Zhang G, Zhang W, Yang X, Zhang S, Ju J, Zhang C (2011) Lobophorins E and F, new spirotetronate antibiotics from a South China Sea-derived Streptomyces sp. SCSIO 01127. J Antibiot 64:711–716
Raahave D (1974) Paper disk–agar diffusion assay of penicillin in the presence of streptomycin. Antimicrob Agents Chemother 6:603–605
Riedlinger J, Reicke A, Zahner H, Krismer B, Bull AT, Maldonado LA, Ward AC, Goodfellow M, Bister B, Bischoff D, Sussmuth RD, Fiedler HP (2004) Abyssomicins, inhibitors of the para-aminobenzoic acid pathway produced by the marine Verrucosispora strain AB-18-032. J Antibiot 57:271–279
Shirling EB, Gottlieb D (1966) Methods for characterization of Streptomyces species. Int J Syst Bacteriol 16:313–340
Song FH, Dai HQ, Tong YJ, Ren B, Chen CX, Sun N, Liu XY, Bian J, Liu M, Gao H, Liu HW, Chen XP, Zhang LX (2010) Trichodermaketones A–D and 7-O-methylkoninginin D from the marine fungus Trichoderma koningii. J Nat Prod 73:806–810
Song FH, Liu XR, Guo H, Ren B, Chen CX, Piggott AM, Yu K, Gao H, Wang Q, Liu M, Dai HQ, Zhang LX, Capon RJ (2012) Brevianamides with antitubercular potential from a marine-derived isolate of Aspergillus versicolor. Org Lett 14:4770–4773
Sunaryanto R, Marwoto B (2010) Marine actinomycetes screening of Banten West Coast and their antibiotics purification. Biodiversitas 11:176–181
Waitz JA, Horan AC, Kalyanpur M, Lee BK, Loebenberg D, Marquez JA, Miller G, Patel MG (1981) Kijanimicin (Sch 25663), a novel antibiotic produced by Actinomadura kijaniata SCC 1256. Fermentation, isolation, characterization and biological properties. J Antibiot 34:1101–1106
Wang Q, Song FH, Xiao X, Huang P, Li L, Monte A, Abdel-Mageed WM, Wang J, Guo H, He W, Xie F, Dai HQ, Liu MM, Chen CX, Xu H, Liu M, Piggott AM, Liu XT, Capon RJ, Zhang LX (2012) Abyssomicins from the South China Sea deep-sea sediment Verrucosispora sp.: natural thioether Michael addition adducts as antitubercular prodrugs. Angew Chem Int Ed. doi:10.1002/anie.201208801
Wei RB, Xi T, Li J, Wang P, Li FC, Lin YC, Qin S (2011) Lobophorin C and D, new kijanimicin derivatives from a marine sponge-associated actinomycetal strain AZS17. Mar Drugs 9:359–368
World Health Organization (2011) Global tuberculosis control 2011: WHO report 2011. Available at http://www.who.int/tb/publications/global_report/2011/gtbr11_full.pdf
Yu K, Ren B, Wei JL, Chen CX, Song FH, Dai HQ, Zhang LX (2010) Verrucisidin A and B, two prone-type polyketides isolated from a marine derived fungus, Penicillium aurantiogriseum. Mar Drugs 8:2744–2754
Zhang LX, An R, Wang J, Sun N, Zhang S, Hu J, Kuai J (2005) Isolation of novel bioactive compounds from marine microbes. Curr Opin Microbiol 8:276–281
Zhang LX, Yan KZ, Zhang Y, Huang R, Bian J, Zheng CS, Sun HX, Sun N, An R, Min FG, Zhang WB, Zhuo Y, You JL, Song YJ, Yu ZY, Liu ZH, Yang HK, Gao H, Dai HQ, Zhang XL, Wang J, Fu CZ, Pei G, Liu JT, Zhang S, Goodfellow M, Jiang YY, Kuai J, Zhou GC, Chen XP (2007) High throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proc Natl Acad Sci 104:4606–4611
Acknowledgments
This work was supported in part by the National Program on Key Basic Research Project (973 program, 2013CB734000, 2012CB725200, 2012CB721006), the National Natural Science Foundation of China (81102356, 30973665, 30901849, 30911120483, 30911120484, 81102369, and 31050110430), the CAS Pillar Program (XDA04074000), the Ministry of Science and Technology of China (2011ZX11102-011-11, 2007DFB31620), the General and Special Program of China Postdoctoral Science Foundation, Genzyme, Sanofi company, the Global Alliance for TB Drug Development (TB Alliance), the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 312184. L.Z. is an Awardee of the National Distinguished Young Scholar Program in China.
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Caixia Chen, Jian Wang, and Hui Guo contributed equally to this paper.
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Chen, C., Wang, J., Guo, H. et al. Three antimycobacterial metabolites identified from a marine-derived Streptomyces sp. MS100061. Appl Microbiol Biotechnol 97, 3885–3892 (2013). https://doi.org/10.1007/s00253-012-4681-0
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DOI: https://doi.org/10.1007/s00253-012-4681-0