Genetic analysis and manipulation of polyene antibiotic gene clusters as a way to produce more effective antifungal compounds

Antimicrobial Compounds: Current Strategies and New Alternatives

Volumn 9783642404443, Issue , 2014, Pages 177-214

  Letek, Michal ^a,b   Mateos, Luis M ^a   Gil, José A ^a  

^a UNIVERSITY OF LEÓN   (Spain)

^b UNIVERSITY OF ROEHAMPTON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84930260562     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-3-642-40444-3_7     Document Type: Chapter

References (191)

1. Ammann A, Gottlieb D, Brock TD, Carter HE, Whitfield GB (1955) Filipin, an antibiotic effective against fungi. Phytopathology 45:559-563
2. Antonio J, Molinski TF (1993) Screening of marine invertebrates for the presence of ergosterolsensitive antifungal compounds. J Nat Prod 56:54-61
3. Aparicio JF, Colina AJ, Ceballos E, Martin JF (1999) The biosynthetic gene cluster for the 26-membered ring polyene macrolide pimaricin. A new polyketide synthase organization encoded by two subclusters separated by functionalization genes. J Biol Chem 274:10133-10139
4. Aparicio JF, Fouces R, Mendes MV, Olivera N, Martin JF (2000) A complex multienzyme system encoded by five polyketide synthase genes is involved in the biosynthesis of the 26-membered polyene macrolide pimaricin in Streptomyces natalensis. Chem Biol 7:895-905
5. Aparicio JF, Caffrey P, Gil JA, Zotchev SB (2003) Polyene antibiotic biosynthesis gene clusters. Appl Microbiol Biotechnol 61:179-188
6. Aparicio JF, Mendes MV, Anton N, Recio E, Martin JF (2004) Polyene macrolide antibiotic biosynthesis. Curr Med Chem 11:1645-1656
7. Arcamone F, Bertazzoli C, Canevazzi G, di Marco A, Ghione M, Grein A (1957) La etrucomicina, nuovo antibiotico antifungino prodotto dallo Streptomyces lucensis n. sp. Giorn Microbiol 4:119-128
8. Arhin FF, Vining LC (1993) Organization of the genes encoding p-aminobenzoic acid synthetase from Streptomyces lividans 1326. Gene 126:129-133
9. Barke J, Seipke RF, Gruschow S, Heavens D, Drou N, Bibb MJ, Goss RJ, Yu DW, Hutchings MI (2010) A mixed community of actinomycetes produce multiple antibiotics for the fungus farming ant Acromyrmex octospinosus. BMC Biol 8 (109-7007-8-109)
10. Bohlmann F, Dehmlow EV, Neuhahn HJ, Brandt R, Bethke H (1970) New heptaene macrolides. II. Basic skeleton, arrangement of functional groups, and structure of aglycones. Tetrahedron 26:2199-2207
11. Borgos SEF, Tsan P, Sletta H, Ellingsen TE, Lancelin J, Zotchev SB (2006) Probing the structure-function relationship of polyene macrolides: engineered biosynthesis of soluble nystatin analogues. J Med Chem 49:2431-2439
12. Borovskii EV, Malyshkina MA, Kotenko TV, Solov'ev SN (1965) Mycoheptin, a new antifungal antibiotic from the group of nonaromatic heptains. Antibiotiki 10:776-780
13. Borowski E, Schaffner CP, Lechevalier H, Schwarz BS (1961) Perimycin, a novel type of heptaene antifungal antibiotic. Antimicrob Agents Chemother (1961-1970) 1960, 532-538
14. Borowski E, Golik J, Zielinski J, Falkowski L, Kolodziejczyk P, Pawlak J (1978) The structure of mycoheptin, a polyene macrolide antifungal antibiotic. J Antibiot (Tokyo) 31:117-123
15. Bortolo R, Spera S, Guglielmetti G, Cassani G (1993) AB023, novel polyene antibiotics. II. Isolation and structure determination. J Antibiot 46:255-264
16. Brautaset T, Sekurova ON, Sletta H, Ellingsen TE, StrLm AR, Valla S, Zotchev SB (2000) 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
17. Brautaset T, Bruheim P, Sletta H, Hagen L, Ellingsen TE, Strom AR, Valla S, Zotchev SB (2002) Hexaene derivatives of nystatin produced as a result of an induced rearrangement within the nysC polyketide synthase gene in S. noursei ATCC 11455. Chem Biol 9:367-373
18. Brautaset T, Sletta H, Nedal A, Borgos SE, Degnes KF, Bakke I, Volokhan O, Sekurova ON, Treshalin ID (2008) Improved antifungal polyene macrolides via engineering of the nystatin biosynthetic genes in Streptomyces noursei. Chem Biol 15:1198-1206
19. Brautaset T, Sletta H, Degnes KF, Sekurova ON, Bakke I, Volokhan O, Andreassen T, Ellingsen TE, Zotchev SB (2011) New nystatin-related antifungal polyene macrolides with altered polyol region generated via biosynthetic engineering of Streptomyces noursei. Appl Environ Microbiol 77:6636-6643
20. Brown R, Hazen EL, Mason A (1953) Effect of fungicidin (nystatin) in mice injected with lethal mixtures of aureomycin and Candida albicans. Science 117:609-610
21. Bruheim P, Borgos SE, Tsan P, Sletta H, Ellingsen TE, Lancelin JM, Zotchev SB (2004) Chemical diversity of polyene macrolides produced by Streptomyces noursei ATCC 11455 and recombinant strain ERD44 with genetically altered polyketide synthase NysC. Antimicrob Agents Chemother 48:4120-4129
22. Burkholder PR, Ruetzler K (1969) Antimicrobial activity of some marine sponges. Nature 222:983-984
23. Burns J, Holtman DF (1959) Tennecetin: A new antifungal antibiotic. General considerations. Antibiot Chemother (Washington, D C) 9:398-405
24. Byrne B, Carmody M, Gibson E, Rawlings B, Caffrey P (2003) Biosynthesis of deoxyamphotericins and deoxyamphoteronolides by engineered strains of Streptomyces nodosus. Chem Biol 10:1215-1224
25. Caffrey P, Lynch S, Flood E, Finnan S, Oliynyk M (2001) Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes. Chem Biol 8:713-723
26. Caffrey P, Aparicio JF, Malpartida F, Zotchev SB (2008) Biosynthetic engineering of polyene macrolides towards generation of improved antifungal and antiparasitic agents. Curr Top Med Chem 8:639-653
27. Cai P, Kong F, Fink P, Ruppen ME, Williamson RT, Keiko T (2007) Polyene antibiotics from Streptomyces mediocidicus. J Nat Prod 70:215-219
28. Campelo AB, Gil JA (2002) The candicidin gene cluster from Streptomyces griseus IMRU 3570. Microbiology 148:51-59
29. Canedo LM, Costa L, Criado LM, Fernandez Puentes JL, Moreno MA (2000) AB-400, a new tetraene macrolide isolated from Streptomyces costae. J Antibiot 53:623-626 (Tokyo)
30. Cao B, Yao F, Zheng X, Cui D, Shao Y, Zhu C, Deng Z, You D (2012) Genome mining of the biosynthetic gene cluster of the polyene macrolide antibiotic tetramycin and characterization of a P450 monooxygenase involved in the hydroxylation of the tetramycin B polyol segment. ChemBioChem 13:2234-2242
31. Carmody M, Murphy B, Byrne B, Power P, Rai D, Rawlings B, Caffrey P (2005) Biosynthesis of amphotericin derivatives lacking exocyclic carboxyl groups. J Biol Chem 280:34420-34426
32. Carver TJ, Rutherford KM, Berriman M, Rajandream MA, Barrell BG, Parkhill J (2005) ACT: The artemis comparison tool. Bioinformatics 21:3422-3423
33. Castillo UF, Strobel GA, Ford EJ, Hess WM, Porter H, Jensen JB, Albert H, Robison R, Condron MA, Teplow DB, Stevens D, Yaver D (2002) Munumbicins, wide-spectrum antibiotics produced by streptomyces NRRL 30562, endophytic on kennedia nigriscans. Microbiology 148:2675-2685
34. Chakrabarti S, Chandra AL (1982) A new streptomycete and a new polyene antibiotic, acmycin. Folia Microbiol (Prague) 27:167-172
35. Challis GL, Ravel J (2000) Coelichelin, a new peptide siderophore encoded by the Streptomyces coelicolor genome: structure prediction from the sequence of its non-ribosomal peptide synthetase. FEMS Microbiol Lett 187:111-114
36. Chater KF, Bruton CJ (1985) Resistance, regulatory and production genes for the antibiotic methylenomycin are clustered. EMBO J 4:1893-1897
37. Chen S, Huang X, Zhou X, Bai L, He J, Jeong KJ, Lee SY, Deng Z (2003) Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex. Chem Biol 10:1065-1076
38. Cheron M, Cybulska B, Mazerski J, Grzybowska J, Czerwinski A, Borowski E (1988) Quantitative structure-activity relationships in amphotericin B derivatives. Biochem Pharmacol 37:827-836
39. Chung EJ, Lim HK, Kim J, Choi GJ, Park EJ, Lee MH, Chung YR, Lee S (2008) Forest soil metagenome gene cluster involved in antifungal activity expression in Escherichia coli. Appl Environ Microbiol 74:723-730
40. Cortes J, Haydock SF, Roberts GA, Bevitt DJ, Leadlay PF (1990) An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature 348:176-178
41. Criado LM, Martin JF, Gil JA (1993) The pab gene of Streptomyces griseus, encoding paminobenzoic acid synthase, is located between genes possibly involved in candicidin biosynthesis. Gene 126:135-139
42. Currie CR, Scott JA, Summerbell RC, Malloch D (1999) Fungus-growing ants use antibioticproducing bacteria to control garden parasites. Nature (London) 398:701-704
43. Currie CR, Scott JA, Summerbell RC, Malloch D (2003) Fungus-growing ants use antibioticproducing bacteria to control garden parasites. Nature (London, U K) 423, 461
44. Cybulska B, Bolard J, Seksek O, Czerwinski A, Borowski E (1995) Identification of the structural elements of amphotericin B and other polyene macrolide antibiotics of the hepteane group influencing the ionic selectivity of the permeability pathways formed in the red cell membrane. Biochim Biophys Acta 1240:167-178
45. Daniel R (2004) The soil metagenome-A rich resource for the discovery of novel natural products. Curr Opin Biotechnol 15:199-204
46. Davisson JW, Tanner FW Jr, Finlay AC, Solomons IA (1951) Rimocidin, a new antibiotic. Antibiot Chemother (Washington, D C) 1:289-290
47. de Kruijff B, Demel RA (1974) Polyene antibiotic-sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. III. Molecular structure of the polyene antibiotic-cholesterol complexes. Biochim Biophys Acta, Biomembr 339:57-70
48. Donia M, Hamann MT (2003) Marine natural products and their potential applications as antiinfective agents. Lancet Infect Dis 3:338-348
49. Dornberger K, Fuegner R, Bradler G, Thrum H (1971) Tetramycin, a new polyene antibiotic. J Antibiot 24:172-177
50. Dunn MF, Ramirez-Trujillo JA, Hernandez-Lucas I (2009) Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis. Microbiology 155:3166-3175
51. Dutcher JD, Young MB, Sherman JH, Hibbits W, Walters DR (1956) Chemical studies on amphotericin B. I. Preparation of the hydrogenation product and isolation of mycosamine, an acetolysis product. Antibiot Annu 866-869
52. Ehrlich J, Bartz QR, Smith RM, Joslyn DA, Burkholder PR (1947) Chloromycetin, a new antibiotic from a soil actinomycete. Science 106:417
53. Falk R, Domb AJ, Polacheck I (1999) A novel injectable water-soluble amphotericin Barabinogalactan conjugate. Antimicrob Agents Chemother 43:1975-1981
54. Feigin AM (1999) Selective modification of sterol composition of hepatomas: new opportunities for chemotherapy. Med Hypotheses 52:383-388
55. Fukuda T, Kim YP, Iizima K, Tomoda H, Omura S (2003) Takanawaenes, novel antifungal antibiotics produced by Streptomyces sp. K99-5278. II. Structure elucidation. J Antibiot (Tokyo) 56:454-458
56. Gil JA, Hopwood DA (1983) Cloning and expression of a p-aminobenzoic acid synthetase gene of the candicidin-producing Streptomyces griseus. Gene 25:119-132
57. Gil JA, Criado LM, Alegre T, Martin JF (1990) Use of a cloned gene involved in candicidin production to discover new polyene producer Streptomyces strains. FEMS Microbiol Lett 58:15-18
58. Glaser KB, Mayer AM (2009) A renaissance in marine pharmacology: from preclinical curiosity to clinical reality. Biochem Pharmacol 78:440-448
59. Gokhale BB (1963) Hamycin, a new antifungal antibiotic. Arch Dermatol 88:558-560
60. Gonzalez I, Ayuso-Sacido A, Anderson A, Genilloud O (2005) Actinomycetes isolated from lichens: evaluation of their diversity and detection of biosynthetic gene sequences. FEMS Microbiol Ecol 54:401-415
61. Gonzalez DJ, Xu Y, Yang YL, Esquenazi E, Liu WT, Edlund A, Duong T, Du L, Molnar I (2012) Observing the invisible through imaging mass spectrometry, a window into the metabolic exchange patterns of microbes. J Proteomics 75:5069-5076 other authors
62. Gottlieb D, Pote HL (1960) Tetrin, an antifungal antibiotic. Phytopathology 50:817-822
63. Gupta KC (1964) Monicamycin, a new polyene antifungal antibiotic. Antimicrob Agents Chemother (Bethesda) 10:65-67
64. Gupte MD, Kulkarni PR (2002) A study of antifungal antibiotic production by Streptomyces chattanoogensis MTCC 3423 using full factorial design. Lett Appl Microbiol 35:22-26
65. Hacene H, Kebir K, Othmane DS, Lefebvre G (1994) HM17, a new polyene antifungal antibiotic produced by a new strain of Spirillospora. J Appl Bacteriol 77:484-489
66. Haeder S, Wirth R, Herz H, Spiteller D (2009) Candicidin-producing Streptomyces support leafcutting ants to protect their fungus garden against the pathogenic fungus Escovopsis. Proc Natl Acad Sci U S A 106:4742-4746
67. Hamilton-Miller JM (1973) Chemistry and biology of the polyene macrolide antibiotics. Bacteriol Rev 37:166-196
68. Han AR, Shinde PB, Park JW, Cho J, Lee SR, Ban YH, Yoo YJ, Kim EJ, Kim E (2012) Engineered biosynthesis of glycosylated derivatives of narbomycin and evaluation of their antibacterial activities. Appl Microbiol Biotechnol 93:1147-1156 other authors
69. Hansen SH, Thomsen M (1976) Comparison of candicidin, levorin and trichomycin by means of high-performance liquid chromatography. J Chromatogr 123:205-211
70. Hayden EC (2009) Fungus farmers show way to new drugs. Nature 458:558
71. Hazen EL, Brown R (1950) Two antifungal agents produced by a soil actinomycete. Science 112:423
72. Henry-Toulme N, Sarthou P, Seman M, Bolard J (1989) Membrane effects of the polyene antibiotic amphotericin B and of some of its derivatives on lymphocytes. Mol Cell Biochem 91:39-44
73. Hickey RJ, Corum CJ, Hidy PH, Cohen IR, Nager UFB, Kropp E (1952) Ascosin, an antifungal antibiotic produced by a Streptomyces. Antibiot Chemother (Washington, D C) 2:472-483
74. Hopwood D (2007) News feature: A call to arms. Nat Rev Drug Discov 6:8-12
75. Hopwood DA, Sherman DH (1990) Molecular genetics of polyketides and its comparison to fatty acid biosynthesis. Annu Rev Genet 24:37-66
76. Hosoya S, Soeda M, Komatsu N, Okada K, Watanabe S (1953) Studies on trichomycin. II. Antibiotic activities against Trichomonas, Candida, and Treponema pallidum. J Antibiot (Tokyo) 6:92-97
77. Hu Z, Bao K, Zhou X, Zhou Q, Hopwood DA, Kieser T, Deng Z (1994) Repeated polyketide synthase modules involved in the biosynthesis of a heptaene macrolide by Streptomyces sp. FR-008. Mol Microbiol 14:163-172
78. Hutchinson E, Murphy B, Dunne T, Breen C, Rawlings B, Caffrey P (2010) Redesign of polyene macrolide glycosylation: engineered biosynthesis of 19-(O)-perosaminyl-amphoteronolide B. Chem Biol 17:174-182
79. Igarashi M, Ogata K, Miyake A (1956) Streptomyces: An antifungal substance produced by Streptomyces aureofaciens. J Antibiot, Ser B 9:79-80
80. 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
81. Itoh A, Ido J, Iwamoto Y, Goshima E, Miki T, Hasuda K, Hirota H (1990) YS-822A, a new polyene macrolide antibiotic. I. Production, isolation, characterization and biological properties. J Antibiot (Tokyo) 43:948-955
82. Jakowska S, Nigrelli RF (1960) Antimicrobial substances from sponges. Ann N Y Acad Sci 90:913-916
83. Jorgensen H, Fjaervik E, Hakvag S, Bruheim P, Bredholt H, Klinkenberg G, Ellingsen TE, Zotchev SB (2009) Candicidin biosynthesis gene cluster is widely distributed among Streptomyces spp. isolated from the sediments and the neuston layer of the Trondheim Fjord, Norway. Appl Environ Microbiol 75:3296-3303
84. Joseph B, Sankarganesh P, Edwin BT, Raj SJ (2012) Endophytic streptomycetes from plants with novel green chemistry: review. Int J Biol Chem 6:42-52
85. Jung WS, Han AR, Hong J, Sung J, Park SR, Choi CY, Park JW, Yoon YJ (2007) Bioconversion of 12-, 14-, and 16-membered ring aglycones to glycosylated macrolides in an engineered strain of Streptomyces venezuelae. Appl Microbiol Biotechnol 76:1373-1381
86. Kakirde KS, Parsley LC, Liles MR (2010) Size does matter: Application-driven approaches for soil metagenomics. Soil Biol Biochem 42:1911-1923
87. Kalasz H, Szell V, Gyimesi J, Magyar K, Horvath I, Szabo I (1972) Antibiotics produced by Streptomyces. IX. Heptafungin-A, a new heptaene macrolide antibiotic. Acta Microbiol 19:111-120
88. Kim BG, Lee MJ, Seo J, Hwang YB, Lee MY, Han K, Sherman DH, Kim ES (2009) Identification of functionally clustered nystatin-like biosynthetic genes in a rare actinomycetes, Pseudonocardia autotrophica. J Ind Microbiol Biotechnol 36:1425-1434
89. Kim D, Moon K, Kim S, Park S, Park S, Lee SK, Oh K, Shin J, Oh D (2012) Bahamaolides A and B, antifungal polyene polyol macrolides from the marine actinomycete Streptomyces sp. J Nat Prod 75:959-967
90. Kiplimo JJ, Everia CA, Koorbanally NA (2011) Novel polyene from Vernonia urticifolia (Asteraceae). J Med Plants Res 5:4202-4211
91. Komaki H, Izumikawa M, Ueda J, Nakashima T, Khan S, Takagi M, Shin-ya K (2009) Discovery of a pimaricin analog JBIR-13, from Streptomyces bicolor NBRC 12746 as predicted by sequence analysis of type I polyketide synthase gene. Appl Microbiol Biotechnol 83:127-133
92. Komori T (1990) Trichomycin B, a polyene macrolide from Streptomyces. J Antibiot (Tokyo) 43:778-782
93. Kozinn PJ, Taschdjian CL, Dragutsky D, Minsky A (1956) Treatment of cutaneous candidiasis in infancy and childhood with nystatin and amphotericin B. Antibiot Annu 128-134
94. Kratky M, Vinsova J (2012) Advances in mycobacterial isocitrate lyase targeting and inhibitors. Curr Med Chem 19:6126-6137
95. Kwon HC, Kauffman CA, Jensen PR, Fenical W (2009) Marinisporolides, polyene-polyol macrolides from a marine actinomycete of the new genus Marinispora. J Org Chem 74:675-684
96. Lechevalier H (1953) Fungicidal antibiotics, produced by actinomycetes, candicidin. Presse Med 61:1327-1328
97. Lee MY, Myeong JS, Park HJ, Han K, Kim ES (2006) Isolation and partial characterization of a cryptic polyene gene cluster in Pseudonocardia autotrophica. J Ind Microbiol Biotechnol 33:84-87
98. Lee MJ, Kong D, Han K, Sherman DH, Bai L, Deng Z, Lin S, Kim ES (2012) Structural analysis and biosynthetic engineering of a solubility-improved and less-hemolytic nystatin-like polyene in Pseudonocardia autotrophica. Appl Microbiol Biotechnol 95:157-168
99. Lei X, Kong L, Zhang C, Liu Q, Yao F, Zhang W, Deng Z, You D (2013) In vivo investigation of the substrate recognition capability and activity affecting amino acid residues of glycosyltransferase FscMI in the biosynthesis of candicidin. Mol BioSyst 9:422-430
100. Li J, Zhao GZ, Chen HH, Wang HB, Qin S, Zhu WY, Xu LH, Jiang CL, Li WJ (2008) Antitumour and antimicrobial activities of endophytic streptomycetes from pharmaceutical plants in rainforest. Lett Appl Microbiol 47:574-580
101. Liu WT, Kersten RD, Yang YL, Moore BS, Dorrestein PC (2011) Imaging mass spectrometry and genome mining via short sequence tagging identified the anti-infective agent arylomycin in Streptomyces roseosporus. J Am Chem Soc 133:18010-18013
102. Lochlainn LN, Caffrey P (2009) Phosphomannose isomerase and phosphomannomutase gene disruptions in Streptomyces nodosus: impact on amphotericin biosynthesis and implications for glycosylation engineering. Metab Eng 11:40-47
103. Lorenz MC, Fink GR (2001) The glyoxylate cycle is required for fungal virulence. Nature 412:83-86
104. Louria DB, Feder N, Emmons CW (1956) Amphotericin B in experimental histoplasmosis and cryptococcosis. Antibiot Annu 870-877
105. Mahmoud YA, Aly MM, Amer SM (2007) Polyenic antifungal (candicidin derivative) from a Streptomyces strain (AFM 105) isolated from marine water. Assiut Univ J Bot 36:61-82
106. Martin JF, Aparicio JF (2009) Enzymology of the polyenes pimaricin and candicidin biosynthesis. Methods Enzymol 459:215-242
107. Mayer AM, Rodriguez AD, Berlinck RG, Fusetani N (2011) Marine pharmacology in 2007-2008: Marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous system, and other miscellaneous mechanisms of action. Comp Biochem Physiol C: Toxicol Pharmacol 153:191-222
108. Mazerski J, Bolard J, Borowski E (1995) Effect of the modifications of ionizable groups of amphotericin B on its ability to form complexes with sterols in hydroalcoholic media. Biochim Biophys Acta, Biomembr 1236:170-176
109. McAlpine JB, Bachmann BO, Piraee M, Tremblay S, Alarco AM, Zazopoulos E, Farnet CM (2005) 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
110. McDaniel LE (1976) Isolation of candihexin-producing strains of Streptomyces viridoflavus. J Antibiot (Tokyo) 29:195-196
111. McDaniel R, Thamchaipenet A, Gustafsson C, Fu H, Betlach M, Ashley G (1999) Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel "unnatural" natural products. Proc Natl Acad Sci U S A 96:1846-1851
112. McGinnis S, Madden TL (2004) BLAST: At the core of a powerful and diverse set of sequence analysis tools. Nucleic Acids Res 32 (web server issue) W20-W25
113. Mendes MV, Recio E, Fouces R, Luiten R, Martin JF, Aparicio JF (2001) Engineered biosynthesis of novel polyenes: A pimaricin derivative produced by targeted gene disruption in Streptomyces natalensis. Chem Biol 8:635-644
114. Mendes MV, Anton N, Martin JF, Aparicio JF (2005) Characterization of the polyene macrolide P450 epoxidase from Streptomyces natalensis that converts de-epoxypimaricin into pimaricin. Biochem J 386:57-62
115. Molinski TF, Dalisay DS, Lievens SL, Saludes JP (2009) Drug development from marine natural products. Nat Rev Drug Discov 8:69-85
116. Mueller UG, Schultz TR, Currie CR, Adams RM, Malloch D (2001) The origin of the attine antfungus mutualism. Q Rev Biol 76:169-197
117. Mulks MH, Nair MG, Putnam AR (1990) In vitro antibacterial activity of faeriefungin, a new broad-spectrum polyene macrolide antibiotic. Antimicrob Agents Chemother 34:1762-1765
118. Mylyshkina MA, Belen'kii BG, Solov'ev SN (1963) Chemical purification of antibiotic 26/1 (levorin). Antibiotiki (Moscow) 8:584-588
119. Naik SR, Desai SK, Nanda RK, Narayanan MS (2007) Fermentation, isolation, purification and biological activity of SJA-95, a heptaene polyene macrolide antibiotic produced by the Streptomyces sp. strain S24. Arzneimittelforschung 57:171-179
120. Nair MG, Putnam AR, Mishra SK, Mulks MH, Taft WH, Keller JE, Miller JR, Zhu PP, Meinhart JD, Lynn DG (1989) Faeriefungin: A new broad-spectrum antibiotic from Streptomyces griseus var. Autotrophicus. J Nat Prod 52:797-809
121. Nedal A, Sletta H, Brautaset T, Borgos SE, Sekurova ON, Ellingsen TE, Zotchev SB (2007) Analysis of the mycosamine biosynthesis and attachment genes in the nystatin biosynthetic gene cluster of Streptomyces noursei ATCC 11455. Appl Environ Microbiol 73:7400-7407
122. Nigrelli RF (1952) Virus and tumors in fishes. Ann N Y Acad Sci 54:1076-1092
123. Nigrelli RF, Jakowska S (1960) Effects of holothurin, a steroid saponin from the bahamian sea cucumber (Actinopyga agassizi), on various biological systems. Ann N Y Acad Sci 90:884-892
124. Nishikiori T, Masuma R, Oiwa R, Katagiri M, Awaya J, Iwai Y, Omura S (1978) Aurantinin, a new antibiotic of bacterial origin. J Antibiot 31:525-532
125. Olano C, Lomovskaya N, Fonstein L, Roll JT, Hutchinson CR (1999) A two-plasmid system for the glycosylation of polyketide antibiotics: bioconversion of epsilon-rhodomycinone to rhodomycin D. Chem Biol 6:845-855
126. Omura S, Ikeda H, Ishikawa J, Hanamoto A, Takahashi C, Shinose M, Takahashi Y, Horikawa H, Nakazawa H (2001) Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites. Proc Natl Acad Sci U S A 98:12215-12220
127. Osada H, Kakeya H, Mori M, Negishi S (2009) New antitumor polyene macrolide RKGS-A2215A, and drugs, cell cycle inhibitors, and antitumor agents containing it. Jpn Kokai Tokkyo Koho 11
128. Osato T, Ueda M, Fukuyama S, Yagishita K, Okami Y, Umezawa H (1955) Production of tertiomycin (a new antibiotic substance), azomycin and eurocidin by S. eurocidicus. J Antibiot (Tokyo) 8:105-109
129. Oura M, Sternberg TH, Wright ET (1955) A new antifungal antibiotic, amphotericin B. Antibiot Annu 3:566-573
130. Pandey RC, Rinehart KLJ (1976) Polyene antibiotics. VII. Carbon-13 nuclear magnetic resonance evidence for cyclic hemiketals in the polyene antibiotics amphotericin B, nystatin A1, tetrin A, tetrin B, lucensomycin, and pimaricin1,2. J Antibiot (Tokyo) 29:1035-1042
131. Pandey RC, Narasimhachari N, Rinehart KL Jr, Millington DS (1972) Polyene antibiotics. IV. Structure of chainin. J Amer Chem Soc 94:4306-4310
132. Paradkar VR, Gupte TE, Joshi AP, Naik SR (1998) A novel Streptoverticillium cinnamonium var scleroticum producing a polyene antibiotic. World J Microbiol Biotechnol 14:705-709
133. Pawlak J, Zielinski J, Golik J, Jereczek E, Borowski E (1980) The structure of lienomycin, a pentaene macrolide antitumor antibiotic. II. The location of the pentaene chromophore and of six isolated double bonds. The complete structure of the antibiotic. J Antibiot 33:998-1004
134. Peiru S, Rodriguez E, Menzella HG, Carney JR, Gramajo H (2008) Metabolically engineered Escherichia coli for efficient production of glycosylated natural products. Microb Biotechnol 1:476-486
135. Perez-Zuniga FJ, Seco EM, Cuesta T, Degenhardt F, Rohr J, Vallin C, Iznaga Y, Perez ME, Gonzalez L, Malpartida F (2004) CE-108, a new macrolide tetraene antibiotic. J Antibiot (Tokyo) 57:197-204
136. Piel J, Hui D, Wen G, Butzke D, Platzer M, Fusetani N, Matsunaga S (2004) Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei. Proc Natl Acad Sci U S A 101:16222-16227
137. Pirt SJ, Pickett SMA, Pickett AM, Vandamme EJ, Bird CW (1981) Antibiotics from the newly isolated Streptomyces elizabethii. I. Production of a polyene antifungal agent (elizabethin) and actinomycin in shake flask cultures. J Chem Technol Biotechnol 31:167-177
138. Pisano MA, Sommer MJ, Brett BP (1987) Hudson river sediments as a source of actinomycetes exhibiting antifungal activity. Appl Microbiol Biotechnol 27:214-217
139. Pontani DR, Sun D, Brown JW, Shahied SI, Plescia OJ, Schaffner CP, Lopez-Berestein G, Sarin PS (1989) Inhibition of HIV replication by liposomal encapsulated amphotericin B. Antiviral Res 11:119-125
140. Power P, Dunne T, Murphy B, Nic Lochlainn L, Rai D, Borissow C, Rawling B, Caffrey P (2008) Engineered synthesis of 7-oxo-and 15-deoxy-15-oxo-amphotericins: insights into structureactivity relationships in polyene antibiotics. Chem Biol 15:78-86
141. Preobrazhenskaya MN, Olsufyeva EN, Solovieva SE, Tevyashova AN, Reznikova MI, Luzikov YN, Terekhova LP, Trenin AS, Galatenko OA (2009) Chemical modification and biological evaluation of new semisynthetic derivatives of 28, 29-didehydronystatin A1 (S44HP), a genetically engineered antifungal polyene macrolide antibiotic. J Med Chem 52:189-196
142. Pushpanathan M, Rajendhran J, Jayashree S, Sundarakrishnan B, Jayachandran S, Gunasekaran P (2012) Identification of a novel antifungal peptide with chitin-binding property from marine metagenome. Protein Pept Lett 19:1289-1296
143. Raatikainen O, Auriola S, Tuomisto J (1991) Identification of aromatic moieties and mycosamine in antifungal heptaenes with high-performance liquid chromatography, high-performance liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. J Chromatogr 585:247-254
144. Rakotoniriana EF, Chataigne G, Raoelison G, Rabemanantsoa C, Munaut F, El Jaziri M, Urveg-Ratsimamanga S, Marchand-Brynaert J, Corbisier AM, Declerck S, Quetin-Leclercq J (2012) Characterization of an endophytic whorl-forming Streptomyces from Catharanthus roseus stems producing polyene macrolide antibiotic. Can J Microbiol 58:617-627
145. Rodriguez E, McDaniel R (2001) Combinatorial biosynthesis of antimicrobials and other natural products. Curr Opin Microbiol 4:526-534
146. Ryu G, Choi WC, Hwang S, Yeo WH, Lee CS, Kim SK (1999) Tetrin C, a new glycosylated polyene macrolide antibiotic produced by Streptomyces sp. GK9244. J Nat Prod 62:917-919
147. Sakuda S, Guce-Bigol U, Itoh M, Nishimura T, Yamada Y (1995) Linearmycin A, a novel linear polyene antibiotic. Tetrahedron Lett 36:2777-2780
148. Sakuda S, Guce-Bigol U, Itoh M, Nishimura T, Yamada Y (1996) Novel linear polyene antibiotics: linearmycins. J Chem Soc, Perkin Trans 1(18):2315-2319
149. Scacchi A, Andriollo N, Cassani G (1995) Detection, characterization and phytotoxic activity of Ab021-A and-b, two new macrolide polyene antibiotics. Pestic Sci 45:49-56
150. Schaffner CP, Gordon HW (1968) The hypocholesterolemic activity of orally administered polyene macrolides. Proc Nat Acad Sci U S 61:36-41
151. Scheffler RJ, Colmer S, Tynan H, Demain AL, Gullo VP (2013) Antimicrobials, drug discovery, and genome mining. Appl Microbiol Biotechnol 97:969-978
152. Schlegel R, Thrum H (1968) Flavomycoine, a new antifungal polyene antibiotic. Experientia 24:11-12
153. Schrey SD, Salo V, Raudaskoski M, Hampp R, Nehls U, Tarkka MT (2007) Interaction with mycorrhiza helper bacterium streptomyces sp. AcH 505 modifies organisation of actin cytoskeleton in the ectomycorrhizal fungus amanita muscaria (fly agaric). Curr Genet 52:77-85
154. Schwecke T, Aparicio JF, Molnar I, Konig A, Khaw LE, Haydock SF, Oliynyk M, Caffrey P, Cortes J, Lester JB (1995) The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. Proc Natl Acad Sci U S A 92:7839-7843
155. Seco EM, Perez-Zuniga FJ, Rolon MS, Malpartida F (2004) Starter unit choice determines the production of two tetraene macrolides, rimocidin and CE-108, in Streptomyces diastaticus var. 108. Chem Biol 11:357-366
156. Seipke RF, Crossman L, Drou N, Heavens D, Bibb MJ, Caccamo M, Hutchings MI (2011a) Draft genome sequence of Streptomyces strain S4, a symbiont of the leaf-cutting ant Acromyrmex octospinosus. J Bacteriol 193:4270-4271
157. Seipke RF, Barke J, Brearley C, Hill L, Yu DW, Goss RJ, Hutchings MI (2011b) A single Streptomyces symbiont makes multiple antifungals to support the fungus farming ant Acromyrmex octospinosus. PLoS ONE 6:e22028
158. Seipke RF, Kaltenpoth M, Hutchings MI (2012) Streptomyces as symbionts: An emerging and widespread theme? FEMS Microbiol Rev 36:862-876
159. Sen R, Ishak HD, Estrada D, Dowd SE, Hong E, Mueller UG (2009) Generalized antifungal activity and 454-screening of Pseudonocardia and Amycolatopsis bacteria in nests of fungusgrowing ants. Proc Natl Acad Sci U S A 106:17805-17810
160. Soler L, Caffrey P, McMahon HEM (2008) Effects of new amphotericin analogues on the scrapie isoform of the prion protein. Biochim Biophys Acta, Gen Subj 1780:1162-1167
161. Soliveri J, Arias M, Laborda F (1987) PA-5 and PA-7, pentaene and heptaene macrolide antibiotics produced by a new isolate of Streptoverticillium from Spanish soil. Appl Microbiol Biotechnol 25:366-371
162. Sowinski P, Gariboldi P, Czerwinski A, Borowski E (1989) The structure of vacidin A, an aromatic heptaene macrolide antibiotic. I. Complete assignment of the proton NMR spectrum and geometry of the polyene chromophore. J Antibiot 42:1631-1638
163. Stephens N, Rawlings B, Caffrey P (2012) Streptomyces nodosus host strains optimized for polyene glycosylation engineering. Biosci Biotechnol Biochem 76:384-387
164. Stephens N, Rawlings B, Caffrey P (2013) Versatility of enzymes catalyzing late steps in polyene 67-121C biosynthesis. Biosci Biotechnol Biochem 77:880-883
165. Stodulkova E, Kuzma M, Hench IB, Cerny J, Kralova J, Novak P, Chudickova M, Savic M, Djokic L, Vasiljevic B, Flieger M (2011) New polyene macrolide family produced by submerged culture of Streptomyces durmitorensis. J Antibiot (Tokyo) 64:717-722
166. Taber WA, Vining LC, Waksman SA (1954) Candidin, a new antifungal antibiotic produced by Streptomyces viridoflavus. Antibiot Chemother (Washington, D C) 4:455-461
167. Takahashi I (1953) A new antifungal substance flavacid; studies on the antibiotic substances from actinomyces, XXVII. J Antibiot (Tokyo) 6:117-121
168. Tewary P, Veena K, Pucadyil TJ, Chattopadhyay A, Madhubala R (2006) The sterol-binding antibiotic nystatin inhibits entry of non-opsonized Leishmania donovani into macrophages. Biochem Biophys Res Commun 339:661-666
169. Thirumalachar MJ, Menon SK (1962) Dermostatin, a new antifungal antibiotic.I. Microbiological studies. Hindustan Antibiot Bull 4:106-108
170. Thirumalachar MJ, Rahalkar PW, Sukapure RS, Gopalkrishnan KS (1964) Aureofungin, a new heptaene antibiotic. I. Microbiological studies. Hindustan Antibiot Bull 6:108-111
171. Thrum H, Kleinwaechter W, Bradler G, Fuegner R (1978) Hexafungin, a new antifungal and antiprotozoal polyene antibiotic. Curr Chemother. In: Proceedings of 10th international congress Chemother 1:226-228
172. Tokala RK, Strap JL, Jung CM, Crawford DL, Salove MH, Deobald LA, Bailey JF, Morra MJ (2002) Novel plant-microbe rhizosphere interaction involving streptomyces lydicus WYEC108 and the pea plant (Pisum sativum). Appl Environ Microbiol 68:2161-2171
173. Tunac JB, McDaniel LE, Schaffner CP (1979) Hydroheptin: A water-soluble polyene macrolide. I. Taxonomy, fermentation and isolation. J Antibiot 32:1223-1229
174. Tytell AA, McCarthy FJ, Fisher WP, Bolhofer WA, Charney J (1955) Fungichromin and fungichromatin: new polyene antifungal agents. Antibiot Annu 2:716-718
175. Uri J, Bekesi I (1958) Flavofungin, a new crystalline antifungal antibiotic: origin and biological properties. Nature (London, U K) 181, 908
176. Vaishnav P, Demain AL (2011) Unexpected applications of secondary metabolites. Biotechnol Adv 29:223-229
177. Veiga M, Fabregas J (1983) Tetrafungin, a new polyene macrolide antibiotic. I. Fermentation, isolation, characterization, and biological properties. J Antibiot (Tokyo) 36:770-775
178. Verona O, Gambogi P (1957) The antimycotic action of nystatin. I. Action upon Aspergillus, Penicillium, and phytopathogenic fungi. Annali Della Sperimentazione Agraria 11:193-209
179. Vertesy L, Aretz W, Ehlers E, Hawser S, Isert D, Knauf M, Kurz M, Schiell M, Vogel M, Wink J (1998) 3874 H1 and H3, novel antifungal heptaene antibiotics produced by Streptomyces sp. HAG 003874. J Antibiot (Tokyo) 51:921-928
180. Wagman GH, Testa RT, Patel M, Marquez JA, Oden EM, Waitz JA, Weinstein MJ (1975) New polyene antifungal antibiotic produced by a species of Actinoplanes. Antimicrob Agents Chemother 7:457-461
181. Wang F, Xu M, Li Q, Sattler I, Lin W (2010) P-aminoacetophenonic acids produced by a mangrove endophyte Streptomyces sp. (strain HK10552). Molecules 15:2782-2790
182. Wasserman HH, Van V, JE, McCaustland DJ, Borowitz IJ, Kamber B (1967) Mycoticins, polyene macrolides from Streptomyces ruber. J Am Chem Soc 89:1535-1536
183. Watrous JD, Phelan VV, Hsu CC, Moree WJ, Duggan BM, Alexandrov T, Dorrestein PC (2013) Microbial metabolic exchange in 3D. ISME J 7:770-780
184. Welscher YM, van Leeuwen MR, de Kruijff B, Dijksterhuis J, Breukink E (2012) Polyene antibiotic that inhibits membrane transport proteins. Proc Natl Acad Sci U S A 109, 11156-11159
185. Xiong ZQ, Zhang ZP, Li JH, Wei SJ, Tu GQ (2012) Characterization of Streptomyces padanus JAU4234, a producer of actinomycin X(2), fungichromin, and a new polyene macrolide antibiotic. Appl Environ Microbiol 78:589-592
186. Xu LH, Fushinobu S, Ikeda H, Wakagi T, Shoun H (2009) Crystal structures of cytochrome P450 105P1 from Streptomyces avermitilis: Conformational flexibility and histidine ligation state. J Bacteriol 191:1211-1219
187. Zhang J, Van L, Steven G, Ju J, Liu W, Dorrestein PC, Li W, Kelleher NL, Shen B (2008) A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis. Proc Natl Acad Sci U S A 105:1460-1465
188. Zielinski J, Jereczek E, Sowinski P, Falkowski L, Rudowski A, Borowski E (1979) The structure of a novel sugar component of polyene macrolide antibiotics: 2,6-dideoxy-L-ribohexopyranose. J Antibiot 32:565-568
189. Zielinski J, Golik J, Pawlak J, Borowski E, Falkowski L (1988) The structure of nystatin A3, a component of nystatin complex. J Antibiot 41:1289-1291
190. Zotchev SB (2003) Polyene macrolide antibiotics and their applications in human therapy. Curr Med Chem 10:211-223
191. Zotchev S, Caffrey P (2009) Genetic analysis of nystatin and amphotericin biosynthesis. Methods Enzymol 459:243-258