Abstract
The type II polyketide synthase (PKS) natural product enterocin (1) was isolated from a mangrove-derived novel species Streptomyces qinglanensis 172205 guided by genome sequence, and its putative biosynthetic gene cluster was revealed. Its natural analogues 5-deoxyenterocin (2) and wailupemycin A–C (3–5) were also identified by tandem mass spectrometry. By feeding experiments with aryl acids, strain 172205 was proved to incorporate partial exogenous starter units into enterocin- and wailupemycin-based analogues, thus being a new and suitable microorganism for engineering unnatural enc-derived polyketide metabolites. In addition, biological assays indicated that enterocin showed obvious inhibitory activity against β-amyloid protein (Aβ1-42) fibrillation and moderate cytotoxicity against HeLa and HepG2 for the first time.
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Babczinski P, Dorgerloh M, Löbberding A, Santel H-J, Schmidt RR, Schmitt P, Wünsche C (1991) Herbicidal activity and mode of action of vulgamycin. Pestic Sci 33:439–446
Chen C, Song F, Wang Q, Abdel-Mageed WM, Guo H, Fu C, Hou W, Dai H, Liu X, Yang N, Xie F, Yu K, Chen R, Zhang L (2012) A marine-derived Streptomyces sp. MS449 produces high yield of actinomycin X2 and actinomycin D with potent anti-tuberculosis activity. Appl Microbiol Biotechnol 95:919–927
Deane CD, Mitchell DA (2014) Lessons learned from the transformation of natural product discovery to a genome-driven endeavor. J Ind Microbiol Biotechnol 41:315–331
Hong K, Gao AH, Xie QY, Gao H, Zhuang L, Lin HP, Yu HP, Li J, Yao XS, Goodfellow M, Ruan JS (2009) Actinomycetes for marine drug discovery isolated from mangrove soils and plants in China. Mar Drugs 7:24–44
Hu H, Lin HP, Xie Q, Li L, Xie XQ, Hong K (2012) Streptomyces qinglanensis sp. nov., isolated from mangrove sediment. Int J Syst Evol Microbiol 62:596–600
Kalaitzis JA (2013) Discovery, biosynthesis, and rational engineering of novel enterocin and wailupemycin polyketide analogues. Methods Mol Biol 1055:171–189
Kalaitzis JA, Izumikawa M, Xiang L, Hertweck C, Moore BS (2003) Mutasynthesis of enterocin and wailupemycin analogues. J Am Chem Soc 125:9290–9291
Kang H, Jensen PR, Fenical W (1996) Isolation of microbial antibiotics from a marine ascidian of the genus Didemnum. J Org Chem 61:1543–1546
Kawashima A, Seto H, Kato M, Uchida K, Otake N (1985) Preparation of fluorinated antibiotics followed by 19F NMR spectroscopy. I. Fluorinated vulgamycins. J Antibiot (Tokyo) 38:1499–1505
Medema MH, Blin K, Cimermancic P, de Jager V, Zakrzewski P, Fischbach MA, Weber T, Takano E, Breitling R (2011) antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res 39:W339–W346
Mitra A, Santra SC, Mukherjee J (2008) Distribution of actinomycetes, their antagonistic behaviour and the physico-chemical characteristics of the world’s largest tidal mangrove forest. Appl Microbiol Biotechnol 80:685–695
Miyairi N, Sakai H, Konomi T, Imanaka H (1976) Enterocin, a new antibiotic taxonomy, isolation and characterization. J Antibiot (Tokyo) 29:227–235
Naiki H, Higuchi K, Hosokawa M, Takeda T (1989) Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, thioflavin T1. Anal Biochem 177:244–249
Piel J, Hertweck C, Shipley PR, Hunt DM, Newman MS, Moore BS (2000) Cloning, sequencing and analysis of the enterocin biosynthesis gene cluster from the marine isolate ‘Streptomyces maritimus’: evidence for the derailment of an aromatic polyketide synthase. Chem Biol 7:943–955
Pistia-Brueggeman G, Hollingsworth RI (2003) The use of the o-nitrophenyl group as a protecting/activating group for 2-acetamido-2-deoxyglucose. Carbohydr Res 338:455–458
Poduslo JF, Wengenack TM, Curran GL, Wisniewski T, Sigurdsson EM, Macura SI, Borowski BJ, Jack CR Jr (2002) Molecular targeting of Alzheimer’s amyloid plaques for contrast-enhanced magnetic resonance imaging. Neurobiol Dis 11:315–329
Seto H, Sato T, Urano S, Uzawa J, Yonehara H (1976) Utilization of 13C-13C coupling in structural and biosynthetic studies. VII1) the structure and biosynthesis of vulgamycin. Tetrahedron Lett 17:4367–4370
Sletta H, Degnes KF, Herfindal L, Klinkenberg G, Fjaervik E, Zahlsen K, Brunsvik A, Nygaard G, Aachmann FL, Ellingsen TE, Doskeland SO, Zotchev SB (2014) Anti-microbial and cytotoxic 1,6-dihydroxyphenazine-5,10-dioxide (iodinin) produced by Streptosporangium sp. DSM 45942 isolated from the fjord sediment. Appl Microbiol Biotechnol 98:603–610
Teufel R, Miyanaga A, Michaudel Q, Stull F, Louie G, Noel JP, Baran PS, Palfey B, Moore BS (2013) Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement. Nature 503:552–556
Valliappan K, Sun W, Li Z (2014) Marine actinobacteria associated with marine organisms and their potentials in producing pharmaceutical natural products. Appl Microbiol Biotechnol 98:7365–7377
Xiang L, Moore BS (2003) Characterization of benzoyl coenzyme A biosynthesis genes in the enterocin-producing bacterium “Streptomyces maritimus”. J Bacteriol 185:399–404
Xiang L, Kalaitzis JA, Moore BS (2004) EncM, a versatile enterocin biosynthetic enzyme involved in Favorskii oxidative rearrangement, aldol condensation, and heterocycle-forming reactions. Proc Natl Acad Sci U S A 101:15609–15614
Xu DB, Ye WW, Han Y, Deng ZX, Hong K (2014a) Natural products from mangrove actinomycetes. Mar Drugs 12:2590–2613
Xu D, Ma M, Liu Y, Zhou T, Wang K, Deng Z, Hong K (2014b) PreQ0 Base, an unusual metabolite with anti-cancer activity from Streptomyces qinglanensis 172205. Anti Cancer Agents Med Chem. doi:10.2174/1871520614666141027144653
Zerikly M, Challis GL (2009) Strategies for the discovery of new natural products by genome mining. Chembiochem 10:625–633
Acknowledgments
This work was partially supported by the China “973” program (2012CB721001), “863” Program (2012AA092201), the National Natural Science Foundation of China (No. 31170467), and the EU FP7 project PharmaSea (312184).
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Xu, DB., Ma, M., Deng, ZX. et al. Genotype-driven isolation of enterocin with novel bioactivities from mangrove-derived Streptomyces qinglanensis 172205. Appl Microbiol Biotechnol 99, 5825–5832 (2015). https://doi.org/10.1007/s00253-015-6574-5
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DOI: https://doi.org/10.1007/s00253-015-6574-5