Abstract
Analyses of biosynthetic gene clusters derived from Streptomyces aculeolatus NRRL 18422 and Streptomyces sp. Eco86 indicated that both microorganisms have similar type I polyketide synthase (PKS) gene clusters with relatively few genes encoding post-PKS elaborative enzymes. However both gene clusters included a sequence coding for a relatively uncommon oxidative enzyme related to Baeyer-Villiger, flavin-type monooxygenases. Screening of culture extracts for compounds with the predicted physicochemical properties of the end products from these loci, led to the isolation of three 5-alkenyl-3,3(2H)-furanones, one (E-837, 1) from the former and two (E-492, 2, E-975, 3) from the latter strain. The structures, confirmed by spectral analyses including MS, and 1D and 2D NMR experiments, were in accord with those predicted by genomic analyses. Baeyer-Villiger type oxidation is postulated to be involved in the formation of the furanone moieties in these molecules. All three new compounds were tested for their electron transport inhibitory activities. They had IC50 values of 1∼4 µg/ml against Ascaris suum NADH-fumarate reductase and 1∼12 µg/ml against bovine heart NADH oxidase.
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Butler MS . The role of natural product chemistry in drug discovery. J Nat Prod 67: 2141–2153 ( 2004)
Zazopoulos E, Huang K, Staffa A, Liu W, Bachmann BO, Nonaka K, Ahlert J, Thorson JS, Shen B, Farnet CM . A genomics-guided approach for discovering and expressing cryptic metabolic pathways. Nat Biotechnol 21: 187–190 ( 2003)
Zazopoulos E, Farnet CM . Improving drug discovery from Microorganisms. Natural Products: Drug Discovery and Therapeutic Medicine; Eds. L. Zhang and A.L. Demain, pp. 95–106 ( 2005)
McAlpine JB, Bachmann BO, Piraee M, Tremblay S, Alarco AM, Zazopoulos E, Farnet CM . Microbial genomics as a guide to drug discovery and structural elucidation: ECO-02301, a novel antifungal agent, as an example. J Nat Prod 68: 493–496 ( 2005)
Fukuda DS, Mynderse JS, Baker PJ, Berry DM, Boeck LD, Yao RC, Mertz FP, Nakatsukasa WM, Mabe J, Ott J, Counter FT, Ensminger PW, Allen NE, Alborn WE Jr, Hobbs JN Jr . A80915, A new antibiotic complex produced by Streptomyces aculeolatus discovery, taxonomy, fermentation, isolation, characterization, and antibacterial evaluation. J Antibiot 43: 623–633 ( 1990)
Banskota AH, McAlpine JB, Zazopoulos E, Sørensen D, Aouidate M, Piraee M, Farnet CF . 46th Annual Meeting of American Society of Pharmacognosy: No. P-143, Corvallis ( 2005)
Brautaset T, Sekurova ON, Sletta H, Ellingsen TE, Strøm AR, Valla S, Zotchev SB . Biosynthesis of the polyene antifungal antibiotic nystatin in Streptomyces noursei ATCC 11455: analysis of the gene cluster and deduction of the biosynthetic pathway. Chem Biol 7: 395–403 ( 2000)
Ōmura S, Ikeda H, Ishikawa J, Hanamoto A, Takahashi C, Shinose M, Takahashi Y, Horikawa H, Nakazawa H, Osonoe T, Kikuchi H, Shiba T, Sakaki Y, Hattori M . Genome sequence of an industrial microorganism Streptomyces avermitilis: Deducing the ability of producing secondary metabolites. Proc Natl Acad Sci USA 98: 12215–12220 ( 2001)
Palaniappan N, Kim BS, Sekiyama Y, Osada H, Reynolds KA . Enhancement and selective production of phoslactomycin B, a protein phosphatase IIa inhibitor, through identification and engineering of the corresponding biosynthetic gene cluster. J Biol Chem 278: 35552–35557 ( 2003)
He J, Hertweck C . Iteration as programmed event during polyketide assembly: molecular analysis of the aureothin biosynthesis gene cluster. Chem Biol 10: 1225–1232 ( 2003)
Prado L, Fernández E, Weißbach U, Blanco G, Quirós LM, Braña AF, Méndez C, Rohr J, Salas JA . Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin. Chem Biol 6: 19–30 ( 1999)
Liu W, Christenson CD, Standage S, Shen B . Biosynthesis of the enediyne antitumor antibiotic C-1027. Science 297: 1170–1173 ( 2002)
Reynolds WF, Enríquez RG . Choosing the best pulse sequences, acquisition parameters, post-acquisition processing strategies, and probes for natural product structure elucidation by NMR spectroscopy. J Nat Prod 65: 221–244 ( 2002)
Kuroda K, Yoshida M, Uosaki Y, Ando K, Kawamoto I, Oishi E, Onuma H, Yamada K, Matsuda Y . AS-183, a novel inhibitor of acyl-CoA: cholesterol acyltransferase produced by Scedosporium sp. SPC-15549. J Antibiot 46: 1196–1202 ( 1996)
Shiomi K, Ui H, Suzuki H, Hatano H, Nagamitsu T, Takano D, Miyadera H, Yamashita T, Kita K, Miyoshi H, Harder A, Tomoda H, Ōmura S . A γ-lactone form nafuredin, nafuredin-γ, also inhibits helminth complex I. J Antibiot 58: 50–55 ( 2005)
Kunze B, Reichenbach H, Müller R, Höfle G . Aurafuron A and B, new bioactive polyketides from Stigmatella aurantiaca and Archangium gephyra (Myxobacteria). J Antibiot 58: 244–251 ( 2005)
National Committee Clinical Laboratory Standards. Approved Standard M27-A. NCCLS, Villanova, PA ( 1997)
Arikan S, Yurdakul P, Hascelik G . Comparison of two methods and three end points in determination of in vitro activity of micafungin against Aspergillus spp. Antimicrob Agents Chemother 47: 2640–2643 ( 2003)
Largis EE, Wang CH, DeVries VG, Schaffer SA . CL277,082: A novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption. J Lipid Res 30: 681–689 ( 1989)
Sliskovic DR, White AD . Therapeutic potential of ACAT inhibitors as lipid lowering and antisclerotic agents. Trends Pharmacol 12: 194–199 ( 1991)
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Banskota, A., McAlpine, J., Sørensen, D. et al. Isolation and Identification of Three New 5-Alkenyl-3,3(2H)-furanones from Two Streptomyces species using a Genomic Screening Approach. J Antibiot 59, 168–176 (2006). https://doi.org/10.1038/ja.2006.24
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DOI: https://doi.org/10.1038/ja.2006.24
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