Dokument

Summary:
Plants, bacteria and fungi provide a plethora of diverse structures derived from the primary as well as the secondary metabolism. Representative substances from secondary metabolite pathways are flavonoids, coumarins, xanthones and indole alkaloids. Although not necessary for the growth and reproduction of the respective organisms, nevertheless these compounds give them an advantage over other organisms in the form of, e.g. attractants or protection agents against natural enemies as well as competitors. The attachment of isoprene units (n  C-5) such as dimethylallyl, geranyl or farnesyl moieties to aromatic secondary metabolites as backbones is a further step in the broad diversification of these compounds. Enzymes of the class of prenyltransferases accomplish this prenyl transfer reaction in nature. The prenylated natural products often exhibit strong pharmacological activities in contrast to their substrates. Therefore, prenylated compounds represent interesting targets for drug development. Investigations on alternative alkyl residues transferable via prenyltransferases, i.e. prenyl diphosphate analogues, could have the potential to play an important role in the understanding of the catalytic mechanism of these enzymes as well as in the finding process of new drugs. As the first project in this thesis, the acceptance of four chemically synthesized alkyl and allyl diphosphates in the presence of three L-tryptophan prenyltransferases (FgaPT2, 5 DMATS, 7 DMATS) was elucidated. Retaining the double bond in β position and performing alterations on the methyl groups of the allyl residue led to regular alkylated products and thereby showed successful utilization of DMAPP analogues. However, depending on the DMAPP analogue, the regiospecificity of the applied prenyltransferases was shifted partially or completely. Furthermore, the enzymes did not catalyze the transfer reaction of alkyl diphosphates onto the L tryptophan scaffold, if no double bond was present or if it was relocated to  position compared to DMAPP. Subsequently, the behavior of cyclic dipeptide prenyltransferases (AnaPT, CdpNPT, CdpC3PT, FtmPT1, BrePT) towards the unnatural alkyl and allyl donors was examined. The cyclic dipeptide prenyltransferases also used the unsaturated DMAPP analogues resulting in the formation of multiple products. Regardless of the prenylation position and orientation for the prenyl attachment (C 2 or C 3; regular or reverse) in the presence of DMAPP, the enzymatic reactions with both DMAPP analogues, i.e. MAPP and 2-pentenyl-PP, yielded a mixture of C2 reverse as well as C3 reverse alkylated diastereomers in different ratios depending on the donor and used enzyme. After the successful alkylation of L tryptophan and tryptophan-containing cyclic dipeptides utilizing simple unnatural allyl DMAPP analogues, the acceptance of the structurally more complex DMAPP analogue benzyl diphosphate was tested. Preliminary investigations showed the successful usage of this benzyl donor by several L tryptophan and cyclic dipeptide prenyltransferases, whereas FgaPT2 showed the highest activity. FgaPT2 also displayed a remarkable promiscuity using tryptophan analogues as substrates and catalyzing a highly regiospecific C5 benzylation. Consequently, the usage of benzyl diphosphate instead of dimethylallyl diphosphate results in a complete shift of the prenylation position from C 4 to C 5. To complete our findings regarding the acceptance of unnatural alkyl and benzyl analogues by prenyltransferases, several tryptophan C5-, C6- and C7-prenylating enzymes of fungal and bacterial origin have been assayed with the three analogues. Depending on the enzyme used, one to four products could be identified from the incubation mixtures. The predominant products were regular C6-alkylated or C6-benzylated derivatives in all cases. Therefore, for the tested tryptophan C5-, C6- and C7-prenylating enzymes, C-6 seemed to be the preferred position for attachment of the alkyl or benzyl moiety. The results obtained during this thesis show that allyl as well as benzyl analogues of DMAPP are potential alternatives for chemoenzymatic FriedelCrafts alkylations of simple indole derivatives and tryptophan-containing cyclic dipeptides and could be used for the production of alkylated compounds.

Bibliographie / References

1. Yu, X., Li, S.-M. (2012). Prenyltransferases of the dimethylallyltryptophan synthase superfamily. Methods Enzymol. 516, 259-278.
2. Reshetilova, T. A., Vinokurova, N. G., Khmelenina, V. N., Kozlovskii, A. G. (1995). The role of roquefortine in the synthesis of alkaloids, meleagrine, glandicolines A and B, and oxaline in Penicillum glandicola and P. atramentosum. Microbiology (Moscow) 64, 27-29.
3. Woodside, A. B., Huang, Z., Poulter, C. D. (1988). Trisammonium geranyl diphosphate. Org. Synth. 66, 211-215.
4. Fan, A., Chen, H., Wu, R., Xu, H., Li, S.-M. (2014). A new member of the DMATS superfamily from Aspergillus niger catalyzes prenylations of both tyrosine and tryptophan derivatives. Appl. Microbiol. Biotechnol. Advance online publication. doi: 10.1007/s00253-014-5872-7.
5. Liebhold, M., Xie, X., Li, S.-M. (2013). Breaking cyclic dipeptide prenyltransferase regioselectivity by unnatural alkyl donors. Org. Lett. 15, 3062-3065.
6. Venugopala, K. N., Rashmi, V., Odhav, B. (2013). Review on natural coumarin lead compounds for their pharmacological activity. Biomed. Res. Int. 2013, 1-14 doi: 10.1155/2013/963248.
7. Wang, F. Q., Zhong, J., Zhao, Y., Xiao, J. F., Liu, J., Dai, M., Zheng, G. Z., Zhang, L., Yu, J., Wu, J. Y., Duan, B. L. (2014). Genome sequencing of high-penicillin producing industrial strain of Penicillium chrysogenum. Bmc Genomics 15, S11-S23 doi: 10.1186/1471-2164-15-S1-S11.
8. Steiger, M. G., Blumhoff, M. L., Mattanovich, D., Sauer, M. (2013). Biochemistry of microbial itaconic acid production. Front. Microbiol. 4, 1-5 doi: 10.3389/fmicb.2013.00023.
9. Manohar, C. S., Raghukumar, C. (2013). Fungal diversity from various marine habitats deduced through culture-independent studies. FEMS Microbiol. Lett. 341, 69-78.
10. Singh, S., Zhang, J. J., Huber, T. D., Sunkara, M., Hurley, K., Goff, R. D., Wang, G. J., Zhang, W., Liu, C. M., Rohr, J., Van Lanen, S. G., Morris, A. J., Thorson, J. S. (2014). Facile Chemoenzymatic Strategies for the Synthesis and Utilization of S-Adenosyl-l-Methionine Analogues. Angew. Chem. Int. Ed. 53, 3965-3969.
11. Weller, R. L., Rajski, S. R. (2006). Design, synthesis, and preliminary biological evaluation of a DNA methyltransferase-directed alkylating agent. Chembiochem 7, 243-245.
12. Maiya, S., Grundmann, A., Li, S.-M., Turner, G. (2006). The fumitremorgin gene cluster of Aspergillus fumigatus: identification of a gene encoding brevianamide F synthetase. Chembiochem. 7, 1062-1069. REFERENCES 189
13. Liu, X., Wang, L., Steffan, N., Yin, W.-B., Li, S.-M. (2009). Ergot alkaloid biosynthesis in Aspergillus fumigatus: FgaAT catalyses the acetylation of fumigaclavine B. Chembiochem 10, 2325-2328.
14. Pockrandt, D., Ludwig, L., Fan, A., Konig, G. M., Li, S.-M. (2012). New insights into the biosynthesis of prenylated xanthones: XptB from Aspergillus nidulans catalyses an O-prenylation of xanthones. Chembiochem 13, 2764-2771. REFERENCES 191
15. Struck, A. W., Thompson, M. L., Wong, L. S., Micklefield, J. (2012). S-Adenosyl-methionine- dependent methyltransferases: Highly versatile enzymes in biocatalysis, biosynthesis and other biotechnological applications. Chembiochem. 13, 2642-2655.
16. Pockrandt, D., Li, S.-M. (2013). Geranylation of cyclic dipeptides by the dimethylallyl transferase AnaPT resulting in a shift of prenylation position on the indole ring. Chembiochem. 14, 2023-2028.
17. Winkelblech, J., Li, S.-M. (2014). Biochemical investigations of two 6-DMATS enzymes from Streptomyces revealing novel features of L-tryptophan prenyltransferases. Chembiochem. 15, 1030- 1039.
18. Kato, H., Yoshida, T., Tokue, T., Nojiri, Y., Hirota, H., Ohta, T., Williams, R. M., Tsukamoto, S. (2007). Notoamides A-D: prenylated indole alkaloids isolated from a marine-derived fungus, Aspergillus sp. Angew. Chem Int. Ed Engl. 46, 2254-2256.
19. Isolation, structure elucidation, and biomimetic total synthesis of versicolamide B, and the isolation of antipodal (-)-stephacidin A and (+)-notoamide B from Aspergillus versicolor NRRL 35600. Angew.
20. Williams, R. M., Stocking, E. M., Sanz-Cervera, J. F. (2000). Biosynthesis of prenylated alkaloids derived from tryptophan. Topics Curr. Chem. 209, 97-173.
21. Oxenbøll, K. (1994), Aspergillus Enzymes and Industrial Uses. In The Genus Aspergillus, ed. K. A. Powell, A. Renwick, and J. F. Peberdy Springer US, pp. 147-154.
22. Jakobsen, M., Cantor, M. D., Jespersen, L. (2002), Production of Bread, Cheese and Meat. In Industrial Applications, ed. H. Osiewacz Springer Berlin Heidelberg, pp. 3-22.
23. Yin, S., Yu, X., Wang, Q., Liu, X. Q., Li, S.-M. (2013a). Identification of a brevianamide F reverse prenyltransferase BrePT from Aspergillus versicolor with a broad substrate specificity towards tryptophan-containing cyclic dipeptides. Appl. Microbiol. Biotechnol. 97, 1649-1660.
24. Tanvir, R., Sajid, I., Hasnain, S. (2014). Biotechnological potential of endophytic actinomycetes associated with Asteraceae plants: isolation, biodiversity and bioactivities. Biotechnol. Lett. 36, 767- 773.
25. Interaction of prenylated chalcones and flavanones from common hop with phosphatidylcholine model membranes. Biochim. Biophys. Acta 1838, 173-184.
26. Teng, K. H., Liang, P. H. (2012). Structures, mechanisms and inhibitors of undecaprenyl diphosphate synthase: A cis-prenyltransferase for bacterial peptidoglycan biosynthesis. Bioorg. Chem. 43, 51-57. REFERENCES 195
27. Zhu, H. Y., Desai, J., Cooper, A. B., Wang, J., Rane, D. F., Kirschmeier, P., Strickland, C., Liu, M., Nomeir, A. A., Girijavallabhan, V. M. (2014). New class of azaheptapyridine FPT inhibitors as potential cancer therapy agents. Bioorg. Med. Chem. Lett. 24, 1228-1231.
28. Yu, X., Zocher, G., Xie, X., Liebhold, M., Schütz, S., Stehle, T., Li, S.-M. (2013). Catalytic mechanism of stereospecific formation of cis-configured prenylated pyrroloindoline diketopiperazines by indole prenyltransferases. Chem. Biol. 20, 1492-1501. REFERENCES 198
29. Yuan, Y., Qiu, X., Nikolic, D., Chen, S. N., Huang, K., Li, G. N., Pauli, G. F., van Breemen, R. B. (2014). Inhibition of human cytochrome P450 enzymes by hops (Humulus lupulus) and hop prenylphenols. Eur. J. Pharm. Sci. 53, 55-61.
30. Kalb, D., Lackner, G., Hoffmeister, D. (2013). Fungal peptide synthetases: an update on functions and specificity signatures. Fungal Biol. Rev. 27, 43-50.
31. Schneider, P., Weber, M., Hoffmeister, D. (2008). The Aspergillus nidulans enzyme TdiB catalyzes prenyltransfer to the precursor of bioactive asterriquinones. Fungal. Genet. Biol. 45, 302-309.
32. Zakaria, I., Ahmat, N., Jaafar, F. M., Widyawaruyanti, A. (2012). Flavonoids with antiplasmodial and cytotoxic activities of Macaranga triloba. Fitoterapia 83, 968-972.
33. Yu, L., Zhang, F., Hu, Z., Ding, H., Tang, H., Ma, Z., Zhao, X. (2014). Novel prenylated bichalcone and chalcone from Humulus lupulus and their quinone reductase induction activities. Fitoterapia 93, 115-120.
34. Suryanarayanan, T. S. (2013). Endophyte research: going beyond isolation and metabolite documentation. Fungal Ecol. 6, 561-568.
35. Yang, M., Li, N., Li, F., Zhu, Q., Liu, X., Han, Q., Wang, Y., Chen, Y., Zeng, X., Lv, Y., Zhang, P., Yang, C., Liu, Z. (2013). Xanthohumol, a main prenylated chalcone from hops, reduces liver damage and modulates oxidative reaction and apoptosis in hepatitis C virus infected Tupaia belangeri. Int. Immunopharmacol. 16, 466-474.
36. Madrid, A., Espinoza, L., Gonzalez, C., Mellado, M., Villena, J., Santander, R., Silva, V., Montenegro, I. (2012). Antifungal study of the resinous exudate and of meroterpenoids isolated from Psoralea glandulosa (Fabaceae). J. Ethnopharmacol. 144, 809-811.
37. Substrate specificities of wild and mutated farnesyl diphosphate synthases: Reactivity of allylic substrate homologs having hydrophilic groups at omega-position. J. Mol. Catal. B: Enzym. 59, 225-230.
38. Substrate specificities of farnesyl diphosphate synthases from Bacillus stearothermophilus and porcine liver with cyclic substrate homologs. J. Mol. Catal. B: Enzym. 60, 186-190.
39. Saikia, S., Nicholson, M. J., Young, C., Parker, E. J., Scott, B. (2008). The genetic basis for indole- diterpene chemical diversity in filamentous fungi. Mycol. Res. 112, 184-199.
40. Dhar, M. K., Koul, A., Kaul, S. (2013). Farnesyl pyrophosphate synthase: a key enzyme in isoprenoid biosynthetic pathway and potential molecular target for drug development. N. Biotechnol. 30, 114-123.
41. Tala, M. F., Wabo, H. K., Zeng, G. Z., Ji, C. J., Tane, P., Tan, N. H. (2013). A prenylated xanthone and antiproliferative compounds from leaves of Pentadesma butyracea. Phytochem. Lett. 6, 326-330.
42. Hymery, N., Masson, F., Barbier, G., Coton, E. (2014). Cytotoxicity and immunotoxicity of cyclopiazonic acid on human cells. Toxicol. In Vitro 28, 940-947.
43. Rudolf, J. D., Poulter, C. D. (2013). Tyrosine O-prenyltransferase SirD catalyzes S-, C-, and N- prenylations on tyrosine and tryptophan derivatives. ACS Chem. Biol. 8, 2707-2714.
44. Nishino, T., Ogura, K., Seto, S. (1972). Substrate specificity of farnesyl pyrophosphate synthetase. J. Am. Chem. Soc. 94, 6849-6853.
45. Edwards, D. J., Gerwick, W. H. (2004). Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase. J. Am. Chem. Soc. 126, 11432-11433.
46. Jost, M., Zocher, G., Tarcz, S., Matuschek, M., Xie, X., Li, S.-M., Stehle, T. (2010). Structure- function analysis of an enzymatic prenyl transfer reaction identifies a reaction chamber with modifiable specificity. J. Am. Chem. Soc. 132, 17849-17858.
47. Scott, P. M., Kennedy, B. P. C. (1976). Analysis of blue cheese for roquefortine and other alkaloids from Penicillium roqueforti. J. Agric. Food Chem. 24, 865-868.
48. Walker, J. R., Rothman, S. C., Poulter, C. D. (2008). Synthesis and evaluation of substrate analogues as mechanism-based inhibitors of type II isopentenyl diphosphate isomerase. J. Org. Chem. 73, 726- 729.
49. Kozlovsky, A. G., Vinokurova, N. G., Adanin, V. M., Burkhardt, G., Dahse, H. M., Gräfe, U. (2000). New diketopiperazine alkaloids from Penicillium fellutanum. J. Nat. Prod. 63, 698-700.
50. Sansom, C. E., Larsen, L., Perry, N. B., Berridge, M. V., Chia, E. W., Harper, J. L., Webb, V. L. (2007). An antiproliferative bis-prenylated quinone from the New Zealand brown alga Perithalia capillaris. J. Nat. Prod. 70, 2042-2044.
51. Chiang, C. C., Cheng, M. J., Huang, H. Y., Chang, H. S., Wang, C. J., Chen, I. S. (2010). Prenyl Coumarins from Fatoua pilosa. J. Nat. Prod. 73, 1718-1722.
52. Hosek, J., Bartos, M., Chudik, S., Dall'acqua, S., Innocenti, G., Kartal, M., Kokoska, L., Kollar, P., Kutil, Z., Landa, P., Marek, R., Zavalova, V., Zemlicka, M., Smejkal, K. (2011). Natural compound cudraflavone B shows promising anti-inflammatory properties in Vitro. J Nat. Prod. 74, 614- 619.
53. Finefield, J. M., Frisvad, J. C., Sherman, D. H., Williams, R. M. (2012). Fungal origins of the bicyclo[2.2.2]diazaoctane ring system of prenylated Indole Alkaloids. J. Nat. Prod. 75, 812-833.
54. Tantapakul, C., Phakhodee, W., Ritthiwigrom, T., Cheenpracha, S., Prawat, U., Deachathai, S., Laphookhieo, S. (2012). Rearranged benzophenones and prenylated xanthones from Garcinia propinqua twigs. J. Nat. Prod. 75, 1660-1664.
55. de los Reyes, C., Zbakh, H., Motilva, V., Zubia, E. (2013). Antioxidant and anti-inflammatory meroterpenoids from the brown alga Cystoseira usneoides. J. Nat. Prod. 76, 621-629.
56. Yin, X., Feng, T., Li, Z. H., Dong, Z. J., Li, Y., Liu, J. K. (2013b). Highly oxygenated meroterpenoids from fruiting bodies of the mushroom Tricholoma terreum. J. Nat. Prod. 76, 1365-1368.
57. Sedmera, P., PospÍšil, S., Novák, J. (1991). New furanonaphthoquinone from Streptomyces cinnamonensis. J. Nat. Prod. 54, 870-872.
58. Chen, J., Morita, H., Wakimoto, T., Mori, T., Noguchi, H., Abe, I. (2012). Prenylation of a nonaromatic carbon of indolylbutenone by a fungal indole prenyltransferase. Org. Lett. 14, 3080-3083.
59. Liebhold, M., Xie, X., Li, S.-M. (2012). Expansion of enzymatic Friedel-Crafts alkylation on indoles: Acceptance of unnatural beta-unsaturated allyl diphospates by dimethylallyl-tryptophan synthases. Org.
60. Ozaki, T., Mishima, S., Nishiyama, M., Kuzuyama, T. (2009). NovQ is a prenyltransferase capable of catalyzing the addition of a dimethylallyl group to both phenylpropanoids and flavonoids. J. Antibiot. (Tokyo) 62, 385-392.
61. Yin, W.-B., Cheng, J., Li, S.-M. (2009a). Stereospecific synthesis of aszonalenins by using two recombinant prenyltransferases. Org. Biomol. Chem. 7, 2202-2207.
62. Steffan, N., Grundmann, A., Afiyatullov, A., Ruan, H., Li, S.-M. (2009). FtmOx1, a non heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase, catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus. Org. Biomol. Chem. 7, 4082-4087.
63. Sunassee, S. N., Davies-Coleman, M. T. (2012). Cytotoxic and antioxidant marine prenylated quinones and hydroquinones. Nat. Prod. Rep. 29, 513-535.
64. Ohara, K., Muroya, A., Fukushima, N., Yazaki, K. (2009). Functional characterization of LePGT1, a membrane-bound prenyltransferase involved in the geranylation of p-hydroxybenzoic acid. Biochem.
65. Denning, D. W. (1998). Invasive aspergillosis. Clin. Infect. Dis. 26, 781-803.
66. Veyisoglu, A., Sahin, N. (2014). Streptomyces hoynatensis sp. nov., isolated from deep marine sediment. Int. J. Syst. Evol. Microbiol. 64, 819-826.
67. Grundmann, A., Li, S.-M. (2005). Overproduction, purification and characterization of FtmPT1, a brevianamide F prenyltransferase from Aspergillus fumigatus. Microbiology 151, 2199-2207.
68. Shen, G., Huhman, D., Lei, Z., Snyder, J., Sumner, L. W., Dixon, R. A. (2012). Characterization of an isoflavonoid-specific prenyltransferase from Lupinus albus. Plant Physiol. 159, 70-80.
69. Hegarty, J. M., Yang, H. B., Chi, N. C. (2013). UBIAD1-mediated vitamin K2 synthesis is required for vascular endothelial cell survival and development. Development 140, 1713-1719.
70. Ohnogi, H., Kudo, Y., Tahara, K., Sugiyama, K., Enoki, T., Hayami, S., Sagawa, H., Tanimura, Y., Aoi, W., Naito, Y., Kato, I., Yoshikawa, T. (2012). Six new chalcones from Angelica keiskei inducing adiponectin production in 3T3-L1 adipocytes. Biosci. Biotechnol. Biochem. 76, 961-966.
71. Ceryngier, P., Twardowska, K. (2013). Harmonia axyridis (Coleoptera: Coccinellidae) as a host of the parasitic fungus Hesperomyces virescens (Ascomycota: Laboulbeniales, Laboulbeniaceae): A case report and short review. Eur. J. Entomol. 110, 549-557.
72. Vieira, L. M., Kijjoa, A. (2005). Naturally-occurring xanthones: recent developments. Curr. Med.
73. El-Seedi, H. R., El-Ghorab, D. M. H., El-Barbary, M. A., Zayed, M. F., Göransson, U., Larsson, S., Verpoorte, R. (2009). Naturally occurring xanthones; latest investigations: isolation, structure elucidation and chemosystematic significance. Curr. Med. Chem. 16, 2581-2626.
74. El-Seedi, H. R., El-Barbary, M. A., El-Ghorab, D. M. H., Bohlin, L., Borg-Karlson, A. K., Göransson, U., Verpoorte, R. (2010). Recent insights into the biosynthesis and biological activities of natural xanthones. Curr. Med. Chem. 17, 854-901.
75. Manner, S., Skogman, M., Goeres, D., Vuorela, P., Fallarero, A. (2013). Systematic exploration of natural and synthetic flavonoids for the inhibition of Staphylococcus aureus biofilms. Int. J. Mol. Sci. 14, 19434-19451.
76. Cytotoxic prenylated xanthones from the pericarps of Garcinia mangostana. Molecules. 19, 1820-1827. REFERENCES 197
77. el Khoury, A., Atoui, A. (2010). Ochratoxin A: General Overview and Actual Molecular Status. Toxins 2, 461-493.
78. Serkedjieva, J., Dalgalarrondo, M., Angelova-Duleva, L., Ivanova, I. (2012). Antiviral Potential of A Proteolytic Inhibitor from Streptomyces Chromofuscus 34-1. Biotechnol. Biotec. Eq. 26, 2786-2793.
79. Schatz, A., Bugie, E., Waksman, S. A. (1944). Streptomycin, a substance exhibiting antibiotic activity against gram positive and gram-negative bacteria. Proc. Soc. Exp. Biol. Med. 55, 66-69.
80. Candida albicans cis-prenyltransferase Rer2 is required for protein glycosylation, cell wall integrity and hypha formation. Fungal Genet. Biol. 69C, 1-12.
81. Gholami, O., Jeddi-Tehrani, M., Iranshahi, M., Zarnani, A. H., Ziai, S. A. (2013). Umbelliprenin from Ferula szowitsiana Activates both Intrinsic and Extrinsic Pathways of Apoptosis in Jurkat T-CLL cell line. Iran J. Pharm. Res. 12, 371-376.
82. Scheckhuber, C. Q., Veenhuis, M., van der Klei, I. J. (2013). Improving penicillin biosynthesis in Penicillium chrysogenum by glyoxalase overproduction. Metab. Eng. 18, 36-43.
83. Post, J., van Deenen, N., Fricke, J., Kowalski, N., Wurbs, D., Schaller, H., Eisenreich, W., Huber, C., Twyman, R. M., Prufer, D., Gronover, C. S. (2012). Laticifer-Specific cis-Prenyltransferase Silencing Affects the Rubber, Triterpene, and Inulin Content of Taraxacum brevicorniculatum. Plant Physiol. 158, 1406-1417.
84. Raju, R., Piggott, A. M., Huang, X. C., Capon, R. J. (2011). Nocardioazines: a novel bridged diketopiperazine scaffold from a marine-derived bacterium inhibits p-glycoprotein. Org. Lett. 13, 2770- 2773.
85. New cytotoxic naphthopyrane derivatives from Adenaria floribunda. J. Nat. Prod. 67, 451-453.
86. Schuller, J. M., Zocher, G., Liebhold, M., Xie, X., Stahl, M., Li, S.-M., Stehle, T. (2012). Structure and catalytic mechanism of a cyclic dipeptide prenyltransferase with broad substrate promiscuity. J. Mol. Biol. 422, 87-99.
87. Inducible nitric oxide synthase and cyclooxygenase-2 participate in anti-inflammatory activity of imperatorin from Glehnia littoralis. J. Agric. Food Chem. 60, 1673-1681.
88. Chooi, Y. H., Fang, J., Liu, H., Filler, S. G., Wang, P., Tang, Y. (2013). Genome mining of a prenylated and immunosuppressive polyketide from pathogenic fungi. Org. Lett. 15, 780-783.
89. Mojarrab, M., Delazar, A., Moghadam, S. B., Nazemiyeh, H., Nahar, L., Kumarasamy, Y., Asnaashari, S., Hadjiakhoondi, A., Sarker, S. D. (2011). Armenin and isoarmenin--two prenylated coumarins from the aerial parts of Artemisia armeniaca. Chem. Biodivers. 8, 2097-2103.
90. Webster, J., Weber, R., (2007). Introduction to fungi, 3rd ed. Cambridge, UK: Cambridge University Press.
91. Karaffa, L., Kubicek, C. P. (2003). Aspergillus niger citric acid accumulation: do we understand this well working black box? Appl. Microbiol. Biotechnol. 61, 189-196.
92. Gliszczynska, A., Brodelius, P. E. (2012). Sesquiterpene coumarins. Phytochem. Rev. 11, 77-96.
93. Peng, J., Zhang, X. Y., Tu, Z. C., Xu, X. Y., Qi, S. H. (2013). Alkaloids from the deep-sea-derived fungus Aspergillus westerdijkiae DFFSCS013. J. Nat. Prod. 76, 983-987.
94. Characterization of a single gene cluster responsible for methylpendolmycin and pendolmycin biosynthesis in the deep sea bacterium Marinactinospora thermotolerans. Chembiochem 13, 547-552.
95. Diversity of actinomycetes isolated from Challenger Deep sediment (10,898 m) from the Mariana Trench. Extremophiles 10, 181-189.
96. Nout, M. J. R., Aidoo, K. E. (2002), Asian Fungal Fermented Food. In Industrial Applications, ed. H.
97. Wierenga, R. K., Kapetaniou, E. G., Venkatesan, R. (2010). Triosephosphate isomerase: a highly evolved biocatalyst. Cell. Mol. Life Sci. 67, 3961-3982.
98. Stec, E., Li, S.-M. (2012). Mutagenesis and biochemical studies on AuaA confirmed the importance of the two conserved aspartate-rich motifs and suggested difference in the amino acids for substrate binding in membrane-bound prenyltransferases. Arch. Microbiol. 194, 589-595.
99. Kremer, A., Li, S.-M. (2008). Potential of a 7-dimethylallyltryptophan synthase as a tool for production of prenylated indole derivatives. Appl. Microbiol. Biotechnol. 79, 951-961.
100. Yu, X., Xie, X., Li, S.-M. (2011). Substrate promiscuity of secondary metabolite enzymes: prenylation of hydroxynaphthalenes by fungal indole prenyltransferases. Appl. Microbiol. Biotechnol. 92, 737-748.
101. Takamatsu, S. (2013). Molecular phylogeny reveals phenotypic evolution of powdery mildews (Erysiphales, Ascomycota). J Gen. Plant Pathol. 79, 218-226.
102. Prenylated flavonoid glucoside and two aliphatic alcohol glycosides from the leaves of Euodia meliaefolia (Hance) Benth. J. Nat. Med. 65, 212-216.
103. Winblad, B., Fioravanti, M., Dolezal, T., Logina, I., Milanov, I. G., Popescub, D. C., Solomon, A. (2008). Therapeutic use of Nicergoline. Clin. Drug Investig. 28, 533-552.
104. Wang, Y., Li, Z. L., Bai, J., Zhang, L. M., Wu, X., Zhang, L., Pei, Y. H., Jing, Y. K., Hua, H. M. (2012). 2,5-diketopiperazines from the marine-derived fungus Aspergillus fumigatus YK-7. Chem. Biodivers. 9, 385-393.
105. Kensler, T. W., Roebuck, B. D., Wogan, G. N., Groopman, J. D. (2011). Aflatoxin: A 50-Year Odyssey of Mechanistic and Translational Toxicology. Toxicol. Sci. 120, S28-S48.
106. Coyle, C. M., Cheng, J. Z., O'Connor, S. E., Panaccione, D. G. (2010). An old yellow enzyme gene that controls the branch point between Aspergillus fumigatus and Claviceps purpurea ergot alkaloid pathways. Appl. Environ. Microbiol. 76, 3898-3903.
107. Antibiotics produced by Streptomyces. Braz. J. Infect. Dis. 16, 466-471.
108. Saleh, O., Gust, B., Boll, B., Fiedler, H.-P., Heide, L. (2009). Aromatic prenylation in phenazine biosynthesis: dihydrophenazine-1-carboxylate dimethylallyltransferase from Streptomyces anulatus. J. Biol. Chem. 284, 14439-14447.
109. Tarcz, S., Ludwig, L., Li, S.-M. (2014a). AstPT catalyses both reverse N1-and regular C2-prenylation of a methylated bisindolyl benzoquinone. Chembiochem. 15, 108-116.
110. Stec, E., Pistorius, D., Müller, R., Li, S.-M. (2011). AuaA, a membrane-bound farnesyltransferase from Stigmatella aurantiaca, catalyzes the prenylation of 2-methyl-4-hydroxyquinoline in the biosynthesis of aurachins. Chembiochem 12, 1724-1730.
111. Takahashi, S., Takagi, H., Toyoda, A., Uramoto, M., Nogawa, T., Ueki, M., Sakaki, Y., Osada, H. (2010). Biochemical characterization of a novel indole prenyltransferase from Streptomyces sp. SN-593.
112. Yu, X., Liu, Y., Xie, X., Zheng, X.-D., Li, S.-M. (2012b). Biochemical characterization of indole prenyltransferases: Filling the last gap of prenylation positions by a 5-dimethylallyltryptophan synthase from Aspergillus clavatus. J. Biol. Chem. 287, 1371-1380.
113. Melzer, M., Heide, L. (1994). Characterization of polyprenyldiphosphate: 4-hydroxybenzoate polyprenyltransferase from Escherichia coli. Biochim. Biophys. Acta 1212, 93-102.
114. Yamazaki, M., Fujimoto, H., Kawasaki, T. (1980). Chemistry of tremorogenic metabolites. I.
115. Steffan, N., Unsöld, I. A., Li, S.-M. (2007). Chemoenzymatic synthesis of prenylated indole derivatives by using a 4-dimethylallyltryptophan synthase from Aspergillus fumigatus. Chembiochem 8, 1298-1307.
116. Gale, P. H., Arison, B. H., Folkers, K., Trenner, N. R., Page, A. C. (1963). Coenzyme Q .36. Isolation and Characterization of Coenzyme Q10 (H-10). Biochemistry 2, 196-200.
117. Ikeda, H., Ishikawa, J., Hanamoto, A., Shinose, M., Kikuchi, H., Shiba, T., Sakaki, Y., Hattori, M., Omura, S. (2003). Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis. Nat. Biotechnol. 21, 526-531.
118. Haynes, S. W., Gao, X., Tang, Y., Walsh, C. T. (2013). Complexity generation in fungal peptidyl alkaloid biosynthesis: A two-enzyme pathway to the hexacyclic MDR export pump inhibitor ardeemin.
119. Teh, S. S., Ee, G. C., Mah, S. H., Lim, Y. M., Ahmad, Z. (2013). Cytotoxicity and structure-activity relationships of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora towards nine human cancer cell lines. Molecules. 18, 1985-1994.
120. Chooi, Y. H., Wang, P., Fang, J., Li, Y., Wu, K., Wang, P., Tang, Y. (2012). Discovery and characterization of a group of fungal polycyclic polyketide prenyltransferases. J. Am. Chem. Soc. 134, 9428-9437.
121. Qaisar, S., Zohra, R. R., Aman, A., Ul Qader, S. A. (2014). Enhanced production of cellulose degrading CMCase by newly isolated strain of Aspergillus versicolor. Carbohydr. Polym. 104, 199-203.
122. Schardl, C. L., Panaccione, D. G., Tudzynski, P. (2006). Ergot alkaloids--biology and molecular biology. The Alkaloids, Chem. Biol. 63, 45-86.
123. Flieger, M., Wurst, M., Shelby, R. (1997). Ergot alkaloids -sources, structures and analytical methods. Folia Microbiol. (Praha) 42, 3-30.
124. Wallwey, C., Li, S.-M. (2011). Ergot alkaloids: structure diversity, biosynthetic gene clusters and functional proof of biosynthetic genes. Nat. Prod. Rep. 28, 496-510.
125. Haarmann, T., Rolke, Y., Giesbert, S., Tudzynski, P. (2009). Ergot: from witchcraft to biotechnology. Mol. Plant Pathol. 10, 563-577.
126. Yu, X., Yang, A., Lin, W., Li, S.-M. (2012a). Friedel-Crafts alkylation on indolocarbazoles catalyzed by two dimethylallyltryptophan synthases from Aspergillus. Tetrahedron Lett. 53, 6861-6864.
127. Grundmann, A., Kuznetsova, T., Afiyatullov, S. S., Li, S.-M. (2008). FtmPT2, an N-prenyltransferase from Aspergillus fumigatus, catalyses the last step in the biosynthesis of fumitremorgin B. Chembiochem 9, 2059-2063.
128. Fumitremorgin A from Aspergillus fumigatus. Chem. Pharm. Bull. 28, 245-254.
129. Zeyhle, P., Bauer, J. S., Kalinowski, J., Shin-ya, K., Gross, H., Heide, L. (2014). Genome-based discovery of a novel membrane-bound 1,6-dihydroxyphenazine prenyltransferase from a marine actinomycete. PLoS. One. 9, e99122.
130. Yazaki, K., Kunihisa, M., Fujisaki, T., Sato, F. (2002). Geranyl diphosphate:4-hydroxybenzoate geranyltransferase from Lithospermum erythrorhizon. Cloning and characterization of a key enzyme in shikonin biosynthesis. J. Biol. Chem. 277, 6240-6246.
131. Watve, M. G., Tickoo, R., Jog, M. M., Bhole, B. D. (2001). How many antibiotics are produced by the genus Streptomyces? Arch. Microbiol. 176, 386-390.
132. Hydrophilic anilinogeranyl diphosphate prenyl analogues are ras function inhibitors. Biochemistry 45, 15862-15872.
133. Liu, C., Sun, Z., Shen, S., Lin, L., Li, T., Tian, B., Hua, Y. (2014). Identification and characterization of the geranylgeranyl diphosphate synthase in Deinococcus radiodurans. Lett. Appl. Microbiol. 58, 219- 224.
134. Smetanina, O. F., Kalinovsky, A. I., Khudyakova, Y. V., Pivkin, M. V., Dmitrenok, P. S., Fedorov, S. N., Ji, H., Kwak, J. Y., Kuznetsova, T. A. (2007). Indole alkaloids produced by a marine fungus isolate of Penicillium janthinellum Biourge. J. Nat. Prod. 70, 906-909.
135. Semicochliodinol A and B: inhibitors of HIV-1 protease and EGF-R protein tyrosine kinase related to asterriquinones produced by the fungus Chrysosporium merdarium. J. Antibiot. 50, 395-401.
136. Muehlbacher, M., Poulter, C. D. (1988). Isopentenyl-Diphosphate Isomerase -Inactivation of the Enzyme with Active-Site-Directed Irreversible Inhibitors and Transition-State Analogs. Biochemistry 27, 7315-7328.
137. Kaysser, L., Bernhardt, P., Nam, S. J., Loesgen, S., Ruby, J. G., Skewes-Cox, P., Jensen, P. R., Fenical, W., Moore, B. S. (2012). Merochlorins A-D, cyclic meroterpenoid antibiotics biosynthesized in divergent pathways with vanadium-dependent chloroperoxidases. J. Am. Chem. Soc. 134, 11988- 11991.
138. Corey, E. J., Takeda, M., Kim, C. U. (1972). Method for Selective Conversion of Allylic and Benzylic Alcohols to Halides Under Neutral Conditions. Tetrahedron Lett. 42, 4339-4342.
139. Nakijiquinone s and nakijinol C, new meroterpenoids from a marine sponge of the family spongiidae. Chem. Pharm. Bull. (Tokyo) 62, 209-212.
140. Tsukamoto, S., Umaoka, H., Yoshikawa, K., Ikeda, T., Hirota, H. (2010). Notoamide O, a structurally unprecedented prenylated indole alkaloid, and notoamides P-R from a marine-derived fungus, Aspergillus sp. J. Nat. Prod. 73, 1438-1440.
141. Tsukamoto, S., Kato, H., Samizo, M., Nojiri, Y., Onuki, H., Hirota, H., Ohta, T. (2008). Notoamides F-K, prenylated indole alkaloids isolated from a marine-derived Aspergillus sp. J. Nat. Prod. 71, 2064- 2067.
142. Li, S.-M. (2010). Prenylated indole derivatives from fungi: structure diversity, biological activities, biosynthesis and chemoenzymatic synthesis. Nat. Prod. Rep. 27, 57-78.
143. Simons, R., Gruppen, H., Bovee, T. F. H., Verbruggen, M. A., Vincken, J. P. (2012). Prenylated isoflavonoids from plants as selective estrogen receptor modulators (phytoSERMs). Food Funct. 3, 810- 827. REFERENCES 193
144. Yu, X., Li, S.-M. (2011). Prenylation of flavonoids by using a dimethylallyltryptophan synthase 7- DMATS from Aspergillus fumigatus. Chembiochem 12, 2280-2283.
145. Heide, L. (2009a). Prenyl transfer to aromatic substrates: genetics and enzymology. Curr. Opin. Chem. Biol. 13, 171-179.
146. Yin, W.-B., Yu, X., Xie, X.-L., Li, S.-M. (2010). Preparation of pyrrolo[2,3-b]indoles carrying a ß- configured reverse C3-dimethylallyl moiety by using a recombinant prenyltransferase CdpC3PT. Org. Biomol. Chem. 8, 2430-2438.
147. Osborne, T. C., Obianyo, O., Zhang, X., Cheng, X., Thompson, P. R. (2007). Protein arginine methyltransferase 1: Positively charged residues in substrate peptides distal to the site of methylation are important for substrate binding and catalysis. Biochemistry 46, 13370-13381.
148. Zhang, F. L., Casey, P. J. (1996). Protein prenylation: molecular mechanisms and functional consequences. Annu. Rev. Biochem. 65, 241-269.
149. Gebler, J. C., Poulter, C. D. (1992). Purification and characterization of dimethylallyl tryptophan synthase from Claviceps purpurea. Arch. Biochem. Biophys. 296, 308-313.
150. Liebhold, M., Li, S.-M. (2013). Regiospecific benzylation of tryptophan and derivatives catalyzed by a fungal dimethylallyl transferase. Org. Lett. 15, 5834-5837.
151. Moores, S. L., Schaber, M. D., Mosser, S. D., Rands, E., Ohara, M. B., Garsky, V. M., Marshall, M. S., Pompliano, D. L., Gibbs, J. B. (1991). Sequence Dependence of Protein Isoprenylation. J. Biol. Chem. 266, 14603-14610.
152. Cheng, W., Li, W. (2014). Structural insights into ubiquinone biosynthesis in membranes. Science 343, 878-881.
153. Ruiz-Sanchis, P., Savina, S. A., Albericio, F., Alvarez, M. (2011). Structure, bioactivity and synthesis of natural products with hexahydropyrrolo[2,3-b]indole. Chemistry. 17, 1388-1408.
154. Dolence, J. M., Poulter, C. D. (1996). Synthesis of analogs of farnesyl diphosphate. Tetrahedron 52, 119-130.
155. Heide, L. (2009b). The aminocoumarins: biosynthesis and biology. Nat. Prod. Rep. 26, 1241-1250.
156. Simpkins, N. S., Pavlakos, I., Weller, M. D., Male, L. (2013). The cascade radical cyclisation approach to prenylated alkaloids: synthesis of stephacidin A and notoamide B. Org. Biomol. Chem. 11, 4957-4970.
157. Dixit, V. M., Laskovics, F. M., Noall, W. I., Poulter, C. D. (1981). Tris(Tetra-Normal- Butylammonium) Hydrogen Pyrophosphate -A New Reagent for the Preparation of Allylic Pyrophosphate Esters. J. Org. Chem. 46, 1967-1969.
158. Kim, C. Y., Kim, H. J., Kim, K. M., Oak, M. H. (2013). Vasorelaxant prenylated flavonoids from the roots of Sophora flavescens. Biosci. Biotechnol. Biochem. 77, 395-397.
159. Marahiel, M. A. (2009). Working outside the protein-synthesis rules: insights into non-ribosomal peptide synthesis. J. Pept. Sci. 15, 799-807.
160. Flardh, K., Buttner, M. J. (2009). Streptomyces morphogenetics: dissecting differentiation in a filamentous bacterium. Nat. Rev. Microbiol. 7, 36-49.
161. Stecher, H., Tengg, M., Ueberbacher, B. J., Remler, P., Schwab, H., Griengl, H., Gruber- Khadjawi, M. (2009). Biocatalytic Friedel-Crafts alkylation using non-natural cofactors. Angew. Chem. Int. Ed. 48, 9546-9548.
162. Unsöld, I. A., Li, S.-M. (2006). Reverse prenyltransferase in the biosynthesis of fumigaclavine C in Aspergillus fumigatus: gene expression, purification and characterization of fumigaclavine C synthase FgaPT1. Chembiochem 7, 158-164.
163. Kato, N., Suzuki, H., Takagi, H., Asami, Y., Kakeya, H., Uramoto, M., Usui, T., Takahashi, S., Sugimoto, Y., Osada, H. (2009). Identification of cytochrome P450s required for fumitremorgin biosynthesis in Aspergillus fumigatus. Chembiochem 10, 920-928.
164. Simpson, T. J. (2012). Genetic and biosynthetic studies of the fungal prenylated xanthone shamixanthone and related metabolites in Aspergillus spp. revisited. Chembiochem 13, 1680-1688.
165. Mundt, K., Wollinsky, B., Ruan, H. L., Zhu, T., Li, S.-M. (2012). Identification of the verruculogen prenyltransferase FtmPT3 by a combination of chemical, bioinformatic and biochemical approaches. Chembiochem 13, 2583-2592.
166. Orlowski, J., Machula, K., Janik, A., Zdebska, E., Palamarczyk, G. (2007). Dissecting the role of dolichol in cell wall assembly in the yeast mutants impaired in early glycosylation reactions. Yeast 24, 239-252.
167. Karamat, F., Olry, A., Munakata, R., Koeduka, T., Sugiyama, A., Paris, C., Hehn, A., Bourgaud, F., Yazaki, K. (2014). A coumarin-specific prenyltransferase catalyzes the crucial biosynthetic reaction for furanocoumarin formation in parsley. Plant J. 77, 627-638.
168. Frisvad, J. C., Rank, C., Nielsen, K. F., Larsen, T. O. (2009). Metabolomics of Aspergillus fumigatus. Med. Mycol. 47, S53-S71.
169. Targeted labeling of DNA by methyltransferase-directed transfer of activated groups (mTAG). J. Am. Chem. Soc. 129, 2758-2759.
170. Dalhoff, C., Lukinavicius, G., Klimasauskas, S., Weinhold, E. (2006). Direct transfer of extended groups from synthetic cofactors by DNA methyltransferases. Nat. Chem. Biol. 2, 31-32.
171. Gebler, J. C., Woodside, A. B., Poulter, C. D. (1992). Dimethylallyltryptophan synthase. An enzyme- catalyzed electrophilic aromatic substitution. J. Am. Chem. Soc. 114, 7354-7360.
172. Pham, W., Pantazopoulos, P., Moore, A. (2006). Imaging farnesyl protein transferase using a topologically activated probe. J. Am. Chem. Soc. 128, 11736-11737.
173. Schultz, A. W., Oh, D. C., Carney, J. R., Williamson, R. T., Udwary, D. W., Jensen, P. R., Gould, S. J., Fenical, W., Moore, B. S. (2008). Biosynthesis and structures of cyclomarins and cyclomarazines, prenylated cyclic peptides of marine actinobacterial origin. J Am. Chem Soc. 130, 4507-4516.
174. Li, X. J., Zhang, Q., Zhang, A. L., Gao, J. M. (2012). Metabolites from Aspergillus fumigatus, an endophytic fungus associated with Melia azedarach, and their antifungal, antifeedant, and toxic activities. J. Agric. Food Chem. 60, 3424-3431.
175. Xia, Z. X., Zhang, D. D., Liang, S., Lao, Y. Z., Zhang, H., Tan, H. S., Chen, S. L., Wang, X. H., Xu, H. X. (2012). Bioassay-guided isolation of prenylated xanthones and polycyclic acylphloroglucinols from the leaves of Garcinia nujiangensis. J. Nat. Prod. 75, 1459-1464.
176. Bioactive indole alkaloids and phenyl ether derivatives from a marine-derived Aspergillus sp. Fungus. J. Nat. Prod. 76, 547-553.
177. Lin, T. T., Huang, Y. Y., Tang, G. H., Cheng, Z. B., Liu, X., Luo, H. B., Yin, S. (2014). Prenylated Coumarins: Natural Phosphodiesterase-4 Inhibitors from Toddalia asiatica. J. Nat. Prod. 77, 955-962.
178. Wang, Y., Gloer, J. B., Scott, J. A., Malloch, D. (1995). Terezines A-D: New amino acid-derived bioactive metabolites from the coprophilous fungus Sporormiella teretispora. J. Nat. Prod. 58, 93-99.
179. Wollinsky, B., Ludwig, L., Xie, X., Li, S.-M. (2012b). Breaking the regioselectivity of indole prenyltransferases: identification of regular C3-prenylated hexahydropyrrolo[2,3-b]indoles as side products of the regular C2-prenyltransferase FtmPT1. Org. Biomol. Chem. 10, 9262-9270.
180. Tarcz, S., Xie, X., Li, S.-M. (2014b). Substrate and catalytic promiscuity of secondary metabolite enzymes: O-prenylation of hydroxyxanthones with different prenyl donors by a bisindolyl benzoquinone C-and N-prenyltransferase. RSC Adv. 4, 17986-17992.
181. van Beilen, J. B., Poirier, Y. (2007). Establishment of new crops for the production of natural rubber. Trends Biotechnol. 25, 522-529.
182. Gomez-Escribano, J. P., Song, L. J., Fox, D. J., Yeo, V., Bibb, M. J., Challis, G. L. (2012). Structure and biosynthesis of the unusual polyketide alkaloid coelimycin P1, a metabolic product of the cpk gene cluster of Streptomyces coelicolor M145. Chem. Sci. 3, 2716-2720.
183. Chater, K. F. (1993). Genetics of Differentiation in Streptomyces. Annu. Rev. Microbiol. 47, 685-713.
184. The cytotoxic activities of 7-isopentenyloxycoumarin on 5637 cells via induction of apoptosis and cell cycle arrest in G2/M stage. Daru. 22, 3.
185. Yamamoto, H., Kawai, S., Mayumi, J., Tanaka, T., Iinuma, M., Mizuno, M. (1991). Prenylated Flavanone Production in Callus-Cultures of Sophora-Flavescens Var Angustifolia. Z. Naturforsch. C Bio. Sci. 46, 172-176.
186. Desoubeaux, G., Bailly, E., Chandenier, J. (2014). Diagnosis of invasive pulmonary aspergillosis: Updates and recommendations. Med. Mal. Infect. 44, 89-101.
187. Yin, W.-B., Grundmann, A., Cheng, J., Li, S.-M. (2009b). Acetylaszonalenin biosynthesis in Neosartorya fischeri: Identification of the biosynthetic gene cluster by genomic mining and functional proof of the genes by biochemical investigation. J. Biol. Chem. 284, 100-109.
188. Onguene, P. A., Ntie-Kang, F., Lifongo, L. L., Ndom, J. C., Sippl, W., Mbaze, L. M. (2013). The potential of anti-malarial compounds derived from African medicinal plants, part I: a pharmacological evaluation of alkaloids and terpenoids. Malar. J. 12, 449.
189. Nakagawa, K., Hirota, Y., Sawada, N., Yuge, N., Watanabe, M., Uchino, Y., Okuda, N., Shimomura, Y., Suhara, Y., Okano, T. (2010). Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature 468, 117-121.
190. Chemoenzymatic synthesis and in situ application of S-adenosyl-L-methionine analogs. Org. Biomol.
191. Popjak, G., Rabinowitz, J. L., Baron, J. M. (1969). Artificial substrates for prenyltransferase. Biochem. J. 113, 861-868.
192. Pojer, F., Wemakor, E., Kammerer, B., Chen, H., Walsh, C. T., Li, S.-M., Heide, L. (2003). CloQ, a prenyltransferase involved in clorobiocin biosynthesis. Proc. Natl. Acad. Sci. U. S. A. 100, 2316-2321.
193. Gallagher, R. T., Latch, G. C. M. (1977). Production of the tremorgenic mycotoxins verruculogen and fumitremorgin B by Penicillium piscarium Westling. Appl. Envir. Microbiol. 33, 730-731.
194. Ohnishi, Y., Ishikawa, J., Hara, H., Suzuki, H., Ikenoya, M., Ikeda, H., Yamashita, A., Hattori, M., Horinouchi, S. (2008). Genome sequence of the streptomycin-producing microorganism Streptomyces griseus IFO 13350. J. Bacteriol. 190, 4050-4060.
195. Metzger, U., Schall, C., Zocher, G., Unsöld, I., Stec, E., Li, S.-M., Heide, L., Stehle, T. (2009). The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria. Proc. Natl. Acad. Sci. U. S. A 106, 14309-14314.
196. Schultz, A. W., Lewis, C. A., Luzung, M. R., Baran, P. S., Moore, B. S. (2010). Functional characterization of the cyclomarin/cyclomarazine prenyltransferase CymD directs the biosynthesis of unnatural cyclic peptides. J. Nat. Prod. 73, 373-377.
197. Kumano, T., Richard, S. B., Noel, J. P., Nishiyama, M., Kuzuyama, T. (2008). Chemoenzymatic syntheses of prenylated aromatic small molecules using Streptomyces prenyltransferases with relaxed substrate specificities. Bioorg. Med. Chem. 16, 8117-8126.
198. Tello, M., Kuzuyama, T., Heide, L., Noel, J. P., Richard, S. B. (2008). The ABBA family of aromatic prenyltransferases: broadening natural product diversity. Cell Mol. Life Sci. 65, 1459-1463.
199. Kuzuyama, T., Noel, J. P., Richard, S. B. (2005). Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products. Nature 435, 983-987.
200. Chooi, Y. H., Cacho, R., Tang, Y. (2010). Identification of the viridicatumtoxin and griseofulvin gene clusters from Penicillium aethiopicum. Chem. Biol. 17, 483-494.
201. Sharma, N. K., Pan, J. J., Poulter, C. D. (2010). Type II Isopentenyl Diphosphate Isomerase: Probing the Mechanism with Alkyne/Allene Diphosphate Substrate Analogues. Biochemistry 49, 6228-6233.
202. Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived Aspergillus sp. J. Am. Chem. Soc. 132, 12733-12740.
203. Heaps, N. A., Poulter, C. D. (2011). Synthesis and evaluation of chlorinated substrate analogues for farnesyl diphosphate synthase. J. Org. Chem. 76, 1838-1843. REFERENCES 186
204. Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens. Proc. Natl. Acad. Sci. U. S. A 108, 6258-6263. REFERENCES 188
205. Wang, R., Zheng, W., Yu, H., Deng, H., Luo, M. (2011). Labeling substrates of protein arginine methyltransferase with engineered enzymes and matched S-adenosyl-l-methionine analogues. J. Am.
206. Sanchez, J. F., Entwistle, R., Hung, J. H., Yaegashi, J., Jain, S., Chiang, Y. M., Wang, C. C., Oakley, B. R. (2011). Genome-based deletion analysis reveals the prenyl xanthone biosynthesis pathway in Aspergillus nidulans. J. Am. Chem Soc. 133, 4010-4017. REFERENCES 192
207. Sasaki, K., Tsurumaru, Y., Yamamoto, H., Yazaki, K. (2011). Molecular characterization of a membrane-bound prenyltransferase specific for isoflavone from Sophora flavescens. J. Biol. Chem. 286, 24125-24134.
208. Islam, K., Zheng, W., Yu, H., Deng, H., Luo, M. (2011). Expanding Cofactor Repertoire of Protein Lysine Methyltransferase for Substrate Labeling. ACS Chem. Biol. 6, 679-684.
209. Finefield, J. M., Kato, H., Greshock, T. J., Sherman, D. H., Tsukamoto, S., Williams, R. M. (2011a). Biosynthetic studies of the notoamides: isotopic synthesis of stephacidin a and incorporation into notoamide B and sclerotiamide. Org. Lett. 13, 3802-3805.
210. Finefield, J. M., Sherman, D. H., Tsukamoto, S., Williams, R. M. (2011b). Studies on the biosynthesis of the notoamides: synthesis of an isotopomer of 6-hydroxydeoxybrevianamide e and biosynthetic incorporation into notoamide J. J. Org. Chem. 76, 5954-5958.
211. Peng, J., Hartley, R. M., Fest, G. A., Mooberry, S. L. (2012). Amyrisins A-C, O-prenylated flavonoids from Amyris madrensis. J. Nat. Prod. 75, 494-496.
212. Weber, S. S., Polli, F., Boer, R., Bovenberg, R. A., Driessen, A. J. (2012). Increased penicillin production in Penicillium chrysogenum production strains via balanced overexpression of isopenicillin N acyltransferase. Appl. Environ. Microbiol. 78, 7107-7113.
213. Qian, Q., Schultz, A. W., Moore, B. S., Tanner, M. E. (2012). Mechanistic studies on CymD: A tryptophan reverse N-prenyltransferase. Biochemistry 51, 7733-7739.
214. Zocher, G., Saleh, O., Heim, J. B., Herbst, D. A., Heide, L., Stehle, T. (2012). Structure-based engineering increased the catalytic turnover rate of a novel phenazine prenyltransferase. PLoS. One. 7, e48427.
215. Subramanian, T., Liu, S., Troutman, J. M., Andres, D. A., Spielmann, H. P. (2008). Protein Farnesyltransferase-Catalyzed Isoprenoid Transfer to Peptide Depends on Lipid Size and Shape, not Hydrophobicity. Chembiochem 9, 2872-2882.
216. H., Williams, R. M. (2013a). Synthesis and bioconversions of notoamide T: a biosynthetic precursor to stephacidin A and notoamide B. Org. Lett. 15, 22-25.
217. Subramanian, T., Pais, J. E., Liu, S., Troutman, J. M., Suzuki, Y., Leela, S. K., Fierke, C. A., Andres, D. A., Spielmann, H. P. (2012). Farnesyl diphosphate analogues with aryl moieties are efficient alternate substrates for protein farnesyltransferase. Biochemistry 51, 8307-8319. REFERENCES 194
218. Ozaki, T., Nishiyama, M., Kuzuyama, T. (2013). Novel tryptophan metabolism by a potential gene cluster that is widely distributed among actinomycetes. J. Biol. Chem. 288, 9946-9956.
219. Secondary metabolites from the stem of Ravenia spectabilis Lindl. Pharmacogn. Mag. 9, 76-80.
220. Zheng, C. J., Sohn, M. J., Lee, S., Kim, W. G. (2013). Meleagrin, a new FabI inhibitor from Penicillium chryosogenum with at least one additional mode of action. PLoS. One. 8, e78922.
221. Dolence, J. M., Poulter, C. D. (1995). A Mechanism for Posttranslational Modifications of Proteins by Yeast Protein Farnesyltransferase. Proc. Natl. Acad. Sci. U. S. A 92, 5008-5011.
222. Kato, K., Cox, A. D., Hisaka, M. M., Graham, S. M., Buss, J. E., Der, C. J. (1992). Isoprenoid Addition to Ras Protein Is the Critical Modification for Its Membrane Association and Transforming Activity. Proc. Natl. Acad. Sci. U. S. A 89, 6403-6407.
223. Sasaki, K., Mito, K., Ohara, K., Yamamoto, H., Yazaki, K. (2008). Cloning and characterization of naringenin 8-prenyltransferase, a flavonoid-specific prenyltransferase of Sophora flavescens. Plant Physiol. 146, 1075-1084.
224. Soballe, B., Poole, R. K. (1999). Microbial ubiquinones: multiple roles in respiration, gene regulation and oxidative stress management. Microbiology-Uk 145, 1817-1830.
225. Tsai, H. F., Wang, H., Gebler, J. C., Poulter, C. D., Schardl, C. L. (1995). The Claviceps purpurea gene encoding dimethylallyltryptophan synthase, the committed step for ergot alkaloid biosynthesis. Biochem. Biophys. Res. Commun. 216, 119-125.
226. Ezeama, C. O., Eleje, G. U., Ezeama, N. N., Igwegbe, A. O., Ikechebelu, J. I., Ugboaja, J. O., Ezebialu, I. U., Eke, A. C. (2014). A comparison of prophylactic intramuscular ergometrine and oxytocin for women in the third stage of labor. Int. J. Gynaecol. Obstet. 124, 67-71.
227. Metzger, U., Keller, S., Stevenson, C. E., Heide, L., Lawson, D. M. (2010). Structure and mechanism of the magnesium-independent aromatic prenyltransferase CloQ from the clorobiocin biosynthetic pathway. J. Mol. Biol. 404, 611-626.
228. W., Park, K. H. (2011). Alpha-glucosidase inhibition and antihyperglycemic activity of prenylated xanthones from Garcinia mangostana. Phytochemistry 72, 2148-2154.
229. Sasaki, H., Kashiwada, Y., Shibata, H., Takaishi, Y. (2012). Prenylated flavonoids from Desmodium caudatum and evaluation of their anti-MRSA activity. Phytochemistry 82, 136-142.
230. Lan, W. C., Tzeng, C. W., Lin, C. C., Yen, F. L., Ko, H. H. (2013). Prenylated flavonoids from Artocarpus altilis: antioxidant activities and inhibitory effects on melanin production. Phytochemistry 89, 78-88.
231. Holzapfel, C. W., Hutchison, R. D., Wilkins, D. C. (1970). The isolation and structure of two new indole derivatives from Penicillium cyclopium westling. Tetrahedron 26, 5239-5246.
232. Lu, J. S., Ma, Y. H., Liang, J. J., Xing, Y. Y., Xi, T., Lu, Y. Y. (2012). Aureolic acids from a marine- derived Streptomyces sp WBF16. Microbiol. Res. 167, 590-595.
233. Liu, X. H., Prestwich, G. D. (2004). Didehydrofarnesyl diphosphate: an intrinsically fluorescent inhibitor of protein farnesyltransferase. Bioorg. Med. Chem. Lett. 14, 2137-2140.
234. Wollinsky, B., Ludwig, L., Hamacher, A., Yu, X., Kassack, M. U., Li, S.-M. (2012a). Prenylation at the indole ring leads to a significant increase of cytotoxicity of tryptophan-containing cyclic dipeptides. Bioorg. Med. Chem. Lett. 22, 3866-3869.
235. Sousa, S. F., Fernandes, P. A., Ramos, M. J. (2009). Molecular dynamics simulations on the critical states of the farnesyltransferase enzyme. Bioorg. Med. Chem. 17, 3369-3378.
236. Gallagher, R. T., Wilson, B. J. (1978). Aflatrem, the tremorgenic mycotoxin from Aspergillus flavus. Mycopathologia 66, 183-185.
237. Crameri, R., Garbani, M., Rhyner, C., Huitema, C. (2014). Fungi: the neglected allergenic sources. Allergy 69, 176-185.
238. Kurdelas, R. R., Lima, B., Tapia, A., Feresin, G. E., Gonzalez, S. M., Rodriguez, M. V., Zacchino, S., Enriz, R. D., Freile, M. L. (2010). Antifungal activity of extracts and prenylated coumarins isolated from Baccharis darwinii Hook & Arn. (Asteraceae). Molecules. 15, 4898-4907.
239. Kirk, P. M., Cannon, P. F., Minter, D. W., Stalpers, J. A., eds. (2008). Dictionary of the Fungi, 10th ed. Wallingford, UK: CABI Publishing.

Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten