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Genetic Analysis and Manipulation of Polyene Antibiotic Gene Clusters as a Way to Produce More Effective Antifungal Compounds

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Abstract

The present clinical scenario is one of the growing numbers of immunocompromised patients infected with a variety of fungal pathogens. AIDS, tuberculosis, immunosuppressive therapy, cancer chemotherapy, or the use of broad-spectrum antibiotics contribute to the boost of such patient category. However, progress in the treatment of fungal infections has been slow. Different polyenes and/or azoles are available for the treatment of systemic fungal infections, but it is becoming clear that new and more effective antifungal agents are urgently required. Fortunately, biosynthetic gene clusters for several antifungal polyene macrolides have been characterized, and this opened the way to generate improved antifungal compounds via genetic engineering as well as to understand the molecular mechanisms that regulate polyene production. Here, we will review the history of the discovery of antifungal polyenes, their environmental role, and the strategies currently used for their identification and improvement.

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References

  • Ammann A, Gottlieb D, Brock TD, Carter HE, Whitfield GB (1955) Filipin, an antibiotic effective against fungi. Phytopathology 45:559–563

    CAS  Google Scholar 

  • Antonio J, Molinski TF (1993) Screening of marine invertebrates for the presence of ergosterol-sensitive antifungal compounds. J Nat Prod 56:54–61

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Aparicio JF, Caffrey P, Gil JA, Zotchev SB (2003) Polyene antibiotic biosynthesis gene clusters. Appl Microbiol Biotechnol 61:179–188

    PubMed  CAS  Google Scholar 

  • Aparicio JF, Mendes MV, Anton N, Recio E, Martin JF (2004) Polyene macrolide antibiotic biosynthesis. Curr Med Chem 11:1645–1656

    PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Arhin FF, Vining LC (1993) Organization of the genes encoding p-aminobenzoic acid synthetase from Streptomyces lividans 1326. Gene 126:129–133

    PubMed  CAS  Google Scholar 

  • 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)

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    CAS  Google Scholar 

  • Bortolo R, Spera S, Guglielmetti G, Cassani G (1993) AB023, novel polyene antibiotics. II. Isolation and structure determination. J Antibiot 46:255–264

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Burkholder PR, Ruetzler K (1969) Antimicrobial activity of some marine sponges. Nature 222:983–984

    PubMed  CAS  Google Scholar 

  • Burns J, Holtman DF (1959) Tennecetin: a new antifungal antibiotic. General considerations. Antibiot Chemother (Washington, D C) 9:398–405

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Cai P, Kong F, Fink P, Ruppen ME, Williamson RT, Keiko T (2007) Polyene antibiotics from Streptomyces mediocidicus. J Nat Prod 70:215–219

    PubMed  CAS  Google Scholar 

  • Campelo AB, Gil JA (2002) The candicidin gene cluster from Streptomyces griseus IMRU 3570. Microbiology 148:51–59

    PubMed  CAS  Google Scholar 

  • 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)

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Carver TJ, Rutherford KM, Berriman M, Rajandream MA, Barrell BG, Parkhill J (2005) ACT: The artemis comparison tool. Bioinformatics 21:3422–3423

    Google Scholar 

  • 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

    Google Scholar 

  • Chakrabarti S, Chandra AL (1982) A new streptomycete and a new polyene antibiotic, acmycin. Folia Microbiol (Prague) 27:167–172

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Chater KF, Bruton CJ (1985) Resistance, regulatory and production genes for the antibiotic methylenomycin are clustered. EMBO J 4:1893–1897

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Criado LM, Martin JF, Gil JA (1993) The pab gene of Streptomyces griseus, encoding p-aminobenzoic acid synthase, is located between genes possibly involved in candicidin biosynthesis. Gene 126:135–139

    PubMed  CAS  Google Scholar 

  • Currie CR, Scott JA, Summerbell RC, Malloch D (1999) Fungus-growing ants use antibiotic-producing bacteria to control garden parasites. Nature (London) 398:701–704

    CAS  Google Scholar 

  • Currie CR, Scott JA, Summerbell RC, Malloch D (2003) Fungus-growing ants use antibiotic-producing bacteria to control garden parasites. Nature (London, U K) 423, 461

    Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Daniel R (2004) The soil metagenome–a rich resource for the discovery of novel natural products. Curr Opin Biotechnol 15:199–204

    PubMed  CAS  Google Scholar 

  • Davisson JW, Tanner FW Jr, Finlay AC, Solomons IA (1951) Rimocidin, a new antibiotic. Antibiot Chemother (Washington, D C) 1:289–290

    Google Scholar 

  • 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

    Google Scholar 

  • Donia M, Hamann MT (2003) Marine natural products and their potential applications as anti-infective agents. Lancet Infect Dis 3:338–348

    PubMed  CAS  Google Scholar 

  • Dornberger K, Fuegner R, Bradler G, Thrum H (1971) Tetramycin, a new polyene antibiotic. J Antibiot 24:172–177

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • Ehrlich J, Bartz QR, Smith RM, Joslyn DA, Burkholder PR (1947) Chloromycetin, a new antibiotic from a soil actinomycete. Science 106:417

    PubMed  CAS  Google Scholar 

  • Falk R, Domb AJ, Polacheck I (1999) A novel injectable water-soluble amphotericin B-arabinogalactan conjugate. Antimicrob Agents Chemother 43:1975–1981

    PubMed  CAS  Google Scholar 

  • Feigin AM (1999) Selective modification of sterol composition of hepatomas: new opportunities for chemotherapy. Med Hypotheses 52:383–388

    PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Glaser KB, Mayer AM (2009) A renaissance in marine pharmacology: from preclinical curiosity to clinical reality. Biochem Pharmacol 78:440–448

    PubMed  CAS  Google Scholar 

  • Gokhale BB (1963) Hamycin, a new antifungal antibiotic. Arch Dermatol 88:558–560

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Gottlieb D, Pote HL (1960) Tetrin, an antifungal antibiotic. Phytopathology 50:817–822

    CAS  Google Scholar 

  • Gupta KC (1964) Monicamycin, a new polyene antifungal antibiotic. Antimicrob Agents Chemother (Bethesda) 10:65–67

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Haeder S, Wirth R, Herz H, Spiteller D (2009) Candicidin-producing Streptomyces support leaf-cutting ants to protect their fungus garden against the pathogenic fungus Escovopsis. Proc Natl Acad Sci U S A 106:4742–4746

    PubMed  CAS  Google Scholar 

  • Hamilton-Miller JM (1973) Chemistry and biology of the polyene macrolide antibiotics. Bacteriol Rev 37:166–196

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Hansen SH, Thomsen M (1976) Comparison of candicidin, levorin and trichomycin by means of high-performance liquid chromatography. J Chromatogr 123:205–211

    PubMed  CAS  Google Scholar 

  • Hayden EC (2009) Fungus farmers show way to new drugs. Nature 458:558

    PubMed  Google Scholar 

  • Hazen EL, Brown R (1950) Two antifungal agents produced by a soil actinomycete. Science 112:423

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • Hopwood D (2007) News feature: a call to arms. Nat Rev Drug Discov 6:8–12

    CAS  Google Scholar 

  • Hopwood DA, Sherman DH (1990) Molecular genetics of polyketides and its comparison to fatty acid biosynthesis. Annu Rev Genet 24:37–66

    PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Igarashi M, Ogata K, Miyake A (1956) Streptomyces: an antifungal substance produced by Streptomyces aureofaciens. J Antibiot, Ser B 9:79–80

    CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Jakowska S, Nigrelli RF (1960) Antimicrobial substances from sponges. Ann N Y Acad Sci 90:913–916

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Kakirde KS, Parsley LC, Liles MR (2010) Size does matter: application-driven approaches for soil metagenomics. Soil Biol Biochem 42:1911–1923

    PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Kiplimo JJ, Everia CA, Koorbanally NA (2011) Novel polyene from Vernonia urticifolia (Asteraceae). J Med Plants Res 5:4202–4211

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Komori T (1990) Trichomycin B, a polyene macrolide from Streptomyces. J Antibiot (Tokyo) 43:778–782

    CAS  Google Scholar 

  • 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

    Google Scholar 

  • Kratky M, Vinsova J (2012) Advances in mycobacterial isocitrate lyase targeting and inhibitors. Curr Med Chem 19:6126–6137

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Lechevalier H (1953) Fungicidal antibiotics, produced by actinomycetes, candicidin. Presse Med 61:1327–1328

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Lorenz MC, Fink GR (2001) The glyoxylate cycle is required for fungal virulence. Nature 412:83–86

    PubMed  CAS  Google Scholar 

  • Louria DB, Feder N, Emmons CW (1956) Amphotericin B in experimental histoplasmosis and cryptococcosis. Antibiot Annu 870–877

    Google Scholar 

  • 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

    CAS  Google Scholar 

  • Martin JF, Aparicio JF (2009) Enzymology of the polyenes pimaricin and candicidin biosynthesis. Methods Enzymol 459:215–242

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • McDaniel LE (1976) Isolation of candihexin-producing strains of Streptomyces viridoflavus. J Antibiot (Tokyo) 29:195–196

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Molinski TF, Dalisay DS, Lievens SL, Saludes JP (2009) Drug development from marine natural products. Nat Rev Drug Discov 8:69–85

    PubMed  CAS  Google Scholar 

  • Mueller UG, Schultz TR, Currie CR, Adams RM, Malloch D (2001) The origin of the attine ant-fungus mutualism. Q Rev Biol 76:169–197

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Mylyshkina MA, Belen’kii BG, Solov’ev SN (1963) Chemical purification of antibiotic 26/1 (levorin). Antibiotiki (Moscow) 8:584–588

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Nigrelli RF (1952) Virus and tumors in fishes. Ann N Y Acad Sci 54:1076–1092

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    CAS  Google Scholar 

  • Oura M, Sternberg TH, Wright ET (1955) A new antifungal antibiotic, amphotericin B. Antibiot Annu 3:566–573

    PubMed  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Pandey RC, Narasimhachari N, Rinehart KL Jr, Millington DS (1972) Polyene antibiotics. IV. Structure of chainin. J Amer Chem Soc 94:4306–4310

    CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Pisano MA, Sommer MJ, Brett BP (1987) Hudson river sediments as a source of actinomycetes exhibiting antifungal activity. Appl Microbiol Biotechnol 27:214–217

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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 structure-activity relationships in polyene antibiotics. Chem Biol 15:78–86

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Rodriguez E, McDaniel R (2001) Combinatorial biosynthesis of antimicrobials and other natural products. Curr Opin Microbiol 4:526–534

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Sakuda S, Guce-Bigol U, Itoh M, Nishimura T, Yamada Y (1995) Linearmycin A, a novel linear polyene antibiotic. Tetrahedron Lett 36:2777–2780

    CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    CAS  Google Scholar 

  • Schaffner CP, Gordon HW (1968) The hypocholesterolemic activity of orally administered polyene macrolides. Proc Nat Acad Sci U S 61:36–41

    CAS  Google Scholar 

  • Scheffler RJ, Colmer S, Tynan H, Demain AL, Gullo VP (2013) Antimicrobials, drug discovery, and genome mining. Appl Microbiol Biotechnol 97:969–978

    PubMed  CAS  Google Scholar 

  • Schlegel R, Thrum H (1968) Flavomycoine, a new antifungal polyene antibiotic. Experientia 24:11–12

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Seipke RF, Kaltenpoth M, Hutchings MI (2012) Streptomyces as symbionts: an emerging and widespread theme? FEMS Microbiol Rev 36:862–876

    PubMed  CAS  Google Scholar 

  • 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 fungus-growing ants. Proc Natl Acad Sci U S A 106:17805–17810

    PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Stephens N, Rawlings B, Caffrey P (2012) Streptomyces nodosus host strains optimized for polyene glycosylation engineering. Biosci Biotechnol Biochem 76:384–387

    PubMed  CAS  Google Scholar 

  • Stephens N, Rawlings B, Caffrey P (2013) Versatility of enzymes catalyzing late steps in polyene 67-121C biosynthesis. Biosci Biotechnol Biochem 77:880–883

    PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Taber WA, Vining LC, Waksman SA (1954) Candidin, a new antifungal antibiotic produced by Streptomyces viridoflavus. Antibiot Chemother (Washington, D C) 4:455–461

    Google Scholar 

  • Takahashi I (1953) A new antifungal substance flavacid; studies on the antibiotic substances from actinomyces, XXVII. J Antibiot (Tokyo) 6:117–121

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Thirumalachar MJ, Menon SK (1962) Dermostatin, a new antifungal antibiotic.I. Microbiological studies. Hindustan Antibiot Bull 4:106–108

    CAS  Google Scholar 

  • Thirumalachar MJ, Rahalkar PW, Sukapure RS, Gopalkrishnan KS (1964) Aureofungin, a new heptaene antibiotic. I. Microbiological studies. Hindustan Antibiot Bull 6:108–111

    CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Tunac JB, McDaniel LE, Schaffner CP (1979) Hydroheptin: a water-soluble polyene macrolide. I. Taxonomy, fermentation and isolation. J Antibiot 32:1223–1229

    PubMed  CAS  Google Scholar 

  • Tytell AA, McCarthy FJ, Fisher WP, Bolhofer WA, Charney J (1955) Fungichromin and fungichromatin: new polyene antifungal agents. Antibiot Annu 2:716–718

    CAS  Google Scholar 

  • Uri J, Bekesi I (1958) Flavofungin, a new crystalline antifungal antibiotic: origin and biological properties. Nature (London, U K) 181, 908

    Google Scholar 

  • Vaishnav P, Demain AL (2011) Unexpected applications of secondary metabolites. Biotechnol Adv 29:223–229

    PubMed  CAS  Google Scholar 

  • Veiga M, Fabregas J (1983) Tetrafungin, a new polyene macrolide antibiotic. I. Fermentation, isolation, characterization, and biological properties. J Antibiot (Tokyo) 36:770–775

    CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Zotchev SB (2003) Polyene macrolide antibiotics and their applications in human therapy. Curr Med Chem 10:211–223

    PubMed  CAS  Google Scholar 

  • Zotchev S, Caffrey P (2009) Genetic analysis of nystatin and amphotericin biosynthesis. Methods Enzymol 459:243–258

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the Comisión Interministerial de Ciencia y Tecnología, Plan Nacional de Biotecnología (Spain), and the European Commission (BIO93-0831, BIO96-0583, Alfa II-0313-FA-FCB, and BIO2008-00519).

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  1. Michal Letek

    Present address: Department of Life Sciences, University of Roehamptom, SW15 4JD, London, UK

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  1. Departamento de Biología Molecular, Área de Microbiología, Facultad de Ciencias Biológicas y Ambientales, Universidad de León, 24071, León, Spain

    Michal Letek, Luis M. Mateos & José A. Gil

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  1. Faculty of Pharmacy, Dep Microbiology Parasitology, University of Santiago de Compostela, Santiago de Compostela, Spain

    Tomás G. Villa

  2. Biomedical Center, Lund University, Lund, Sweden

    Patricia Veiga-Crespo

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Letek, M., Mateos, L.M., Gil, J.A. (2014). Genetic Analysis and Manipulation of Polyene Antibiotic Gene Clusters as a Way to Produce More Effective Antifungal Compounds. In: Villa, T., Veiga-Crespo, P. (eds) Antimicrobial Compounds. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40444-3_7

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