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Review

Biosynthetic engineering of polyketide synthases

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Pages 1579-1606 | Published online: 02 Mar 2005

Bibliography

  • KHOSLA C: Natural product biosynthesis: a new interface between enzymology and medicine. Org. Chem. i (2000) 65:8127–8133.
  • BURKART MD: Metabolic engineering - a genetic toolbox for small molecule organic synthesis. Org. Biomol. Chem. i (2003) 1:1–4.
  • NEWMANN DJ, CRAGG GM, SNADER KM: The influence of natural products upon drug discovery. Nat. Prod. Rep. i (2000) 17:215–234.
  • STAUNTON J, WILKINSON B: Combinatorial biosynthesis of polyketides and nonribosomal peptides. Curt: Opin. Chem. Biol. i (2001) 5:159–64.
  • KANEKO T, MCARTHUR H, SUTCLIFFE J: Recent developments in the area of macrolide antibiotics. Expert Opin. Ther. Patents i (1999) 10:403–405.
  • RAWLINGS BJ: Biosynthesis of polyketides (other than actinomycete macrolides). Nat. Prod. Rep. i (1999) 16:425–484.
  • RAWLINGS BJ: Type I polyketide biosynthesis in bacteria (Part A - erythromycin biosynthesis). Nat. Prod Rep. i (2001) 18:190–227.
  • RAWLINGS BJ: Type I polyketide biosynthesis in bacteria (Part B). Nat. Prod Rep. i (2001) 18:231–281.
  • STAUNTON J, WEISSMAN KJ: Polyketide biosynthesis: a millennium review. Nat. Prod. Rep. i (2001) 18:380–416.
  • RIX U, FISHER C, REMSING LL, ROHR J: Modification of post-PKS tailoring steps through combinatorial biosynthesis. Nat. Prod Rep. i (2002) 19:542–580.
  • MENDEZ C, SALAS J: Altering the glycosylation pattern of bioactive compounds. Trends Biotech. i (2001) 19:449–456.
  • RODRIGUEZ L, AGUIRREZABALAGA I, ALLENDE N, BRANA AF, MENDEZ C, SALASJ: Engineering deoxysugar biosynthetic pathways from antibiotic-producing microorganisms: a tool to produce novel glycosylated bioactive compounds. Chem. Biol. i (2002) 9:721–729.
  • BARTON WA, BIGGINS JB, JIANG J, THORSON JS, NIKOLOV DB: Expanding pyrimidine diphosphosugar libraries via structure-based nucleotidylytransferase engineering. Proc. Natl. Acad. Sci. USA i (2002) 99:13397–13402.
  • GAISSER S, LILL R, STAUNTON J, MENDEZ C, SALAS J, LEADLAY PF: Parallel pathways for oxidation of 14-membered polyketide macrolactones in Saccharopolyspora erythraea. Ma. Micro. (2002) 44:771–781.
  • MOORE BS, HOPKE JN: Discovery of a new bacterial polyketide biosynthetic pathway. Chembiochem i (2001) 2:35–38.
  • SHEN B: Polyketide biosynthesis beyond the Type I, II and III polyketide synthase paradigms. Can: Opin. Chem. Biol. i (2003) 7:285–295.
  • KAULMANN U, HERTWECK C: Biosynthesis of polyunsaturated fatty acids by polyketide synthases. Angew. Chem. Int. Ed i (2002) 41:1866–1869.
  • HOPWOOD DA: Genetic contributions to understanding polyketide synthases. Chem. Rev i (1997) 97: 2465–2497.
  • MOORE BS, HERTWECK C: Biosynthesis and attachment of novel bacterial polyketide synthase starter units. Nat. Prod. Rep. i (2002) 19:70–99.
  • HOPWOOD DA, MALPARTIDA F, KIESER HM et al.: i Production of 'hybrid' antibiotics by genetic engineering. Nature i (1985) 314:642–644.
  • BARTEL PL, ZHU CB, LAMPEL JS et al: i Biosynthesis of anthraquinones by interspecies cloning of actinhorodin biosynthetic genes in Streptomyces i - clarification of actinhorodin gene functions. Bacterioi i (1990) 172:4816–4826.
  • MCDANIEL R, EBERT-KHOSLA S, HOPWOOD DA, KHOSLA C: Rational design of aromatic polyketide natural products by recombinant assembly of enzymatic subunits. Nature i (1995) 375:549–554.
  • SHEN B, HUTCHINSON CR: Deciphering the mechanism for the assembly of aromatic polyketides by a bacterial polyketide synthase. Proc. Natl. Acad. Sci. USA i (1996) 96:6000–6604.
  • MEURER G, GERLITZ M, WENDT-PIENKOWSKI E, VINING LC, ROHR J, HUTCHINSON CR: Iterative Type II polyketide synthases, cyclases and ketoreductases exhibit context-dependent behavior in the biosynthesis of linear and angular decapolyketides. Chem. Biol i (1997) 4:433–443.
  • PETKOVIC H, THAMCHAIPENET A, ZHOU LH et al.: i Disruption of an aromatase/cyclase from the oxytetracycline gene cluster of Streptomyces rimacus i results in production of novel polyketides with shorter chain lengths. J. Biol. Chem. i (1999) 274:32829–32834.
  • BISANG C, LONG PF, CORTES J et al: i A chain initiation factor common to both modular and aromatic polyketide synthases. Nature i (1999) 401:502–505.
  • SHEN YM, YOON P, YU TW, FLOSS HG, HOPWOOD D, MOORE BS: Ectopic expression of the minimal whiEpolyketide synthase generates a library of aromatic polyketides of diverse sizes and shapes. Proc. Natl. Acad. Sci. USA i (1999) 96:3622–3627.
  • BAO WL, WENDT-PIENKOWSKI E, HUTCHINSON CR: Reconstitution of the iterative Type II polyketide synthase for tetracenomycin F2 biosynthesis. Biochemistry i (1998) 37:8132–8138.
  • PIEL J, HERTWECK C, SHIPLEY PR, HUNT DM, NEWMAN MS, MOORE BS: Cloning, sequencing and analysis of the enterocin biosynthesis gene cluster from the marine isolate Streptomyces maritimus i evidence for the derailment of an aromatic polyketide synthase. Chem. Biol. i (2000) 7:943–955.
  • METSA-KATELA M, PALMU K, YLIHONKO K, MANTSALA P: Engineering anthracycline biosynthesis towards angucylines. Antimicrob. Agents Chemother. i (2003) 47:1291–1296.
  • TORKKELL S, KUNNARI T, PALMU K, MANTSALA P, HAKALA J, YLIHONKO K: The entire nogalamycin biosynthetic gene cluster of Streptomyces nogalater: i characterization of a 20 kb DNA region and generation of hybrid structures. Ma. Genet. Genomics i (2001) 266:276–88.
  • RICHARDSON M, KHOSLA C: Structure, function and engineering of bacterial aromatic polyketide synthases. In: Comprehensive natural products chemistry i Sankawa U, Barton D, Nakanishi K, Meth-Cohn O (Eds), Elsevier, Oxford, UK (1999)473–494.
  • THIERICKE R, ROHR J: Biological variation of microbial metabolites by precursor-directed biosynthesis. Nat. Prod. Rep. i (1993) 10:265–289.
  • MCARTHUR HAI: A novel avermectin, doramectin - a successful application of mutasynthesis. In: Developments M i Mdustrial microbiology - BMP Hutchinson CR, McAlpine J (Eds), Society for Industrial Microbiology, Fairfax, VA, USA (1998) 43–48.
  • DUTTON CJ, GIBSON SP, GOUDIE AC et al.: i Novel avermectins produced by mutational biosynthesis. Antibia. i (1991) 44:357–365.
  • KHAW LE, BOHM GA, METCALFE S, STAUNTON J, LEADLAY PF: Mutational biosynthesis of novel rapamycins by a strain of Streptomyces hygroscopicusNRRL5491 i disrupted in rapL, i encoding a putative lysine cyclodeaminase. Bacteriol. i (1998) 180:809–814.
  • DU L, SHEN B: Biosynthesis of hybrid peptide-polyketide natural products. Cm: Opin. Drug Discov. Devel i (2001) 4:215–28.
  • NISHIDA H, SAKAKIBARA T, AOKI F et al: i Generation of novel rapamycin structures by microbial manipulations. .1. Antibia. i (1995) 48:657–666.
  • NIELSEN JB, HSU MJ, BYRNE KM, KAPLAN L: Biosynthesis of the immunosuppressant immunomycin: the enzymology of pipecolate incorporation. Biochemistry i (1991) 30:5789–5796.
  • TSUKAMOTO N, CHUCK J-A, LUO G, KAO CM, KHOSLA C, CANE DE: 6-deoxyerythronolide B synthase 1 is specifically acylated by a diketide intermediate at the P-ketoacyl-acyl carrier protein synthase domain of module 2. Biochemistry (1996) i 48:15244–15248.
  • JACOBSEN JR, HUTCHINSON CR, CANE DE, KHOSLA C: Precursor-directed biosynthesis of erythromycin analogs by an engineered polyketide synthase. Science i (1997) 277:367–369.
  • CORTES J, HAYDOCK SF, ROBERTS GA, BEVITT DJ, LEADLAY PF: An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature i (1990) 348:176–178.
  • DONADIO S, STAVER MJ, MCALPINE JB, SWANSON SJ, KATZ L: Modular organization of genes required for complex polyketide biosynthesis. Science i (1991) 252:675–679.
  • DONADIO S, MCALPINE JB, SHELDON PL, JACKSON M, KATZ L: An erythromycin analog produced by reprogramming of polyketide synthesis. Proc. Natl. Acad. Sti. USA i (1993) 90:7119–7123.
  • WEISSMANN KEH, CORTES J, LEADLAY PF: Engineering the erythromycin-producing polyketide synthase: construction of a triketide lactone synthase. Abstracts of the i International Symposium on Actinomycetes, Moscow (1994) i Abstract P 2–02, 154.
  • HUTCHINSON CR: Drug synthesis by genetically engineered microorganisms. Bio-technology i (1994) 12:375-380. (Reference to lecture by PF Leadlay at the Socieh, i for General Microbiology i meeting in Warwick, UK January 1994, 378).
  • CORTES J, WIESMANN KEH, ROBERTS GA, BROWN MJB, STAUNTON J, LEADLAY PF: Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage. Science i (1995) 268:1487–1489.
  • KAO CM, LUO GL, KATZ L, CANE DE, KHOSLA C: Manipulation of macrolide ring size by directed mutagenesis of a modular polyketide synthase. j Am. Chem. Soc. i (1995) 117:9105–9106.
  • KAO CM, LUO GL, KATZ L, CANE DE, KHOSLA C: Engineered biosynthesis of structurally diverse tetraketides by a trimodular polyketide synthase. Am. Chem. Soc. i (1996) 118:9184–9185.
  • OLIYNYK M, BROWN MJB, CORTES J,STAUNTON J, LEADLAY PF: A hybrid modular polyketide synthase obtained by domain swapping. Chem. Biol. i (1996) 3:833–839.
  • KUHSTOSS S, HUBER M, TURNER JR,PASCHAL JW, RAO RN: Production of a novel polyketide through the construction of a hybrid polyketide synthase. Gene i (1996) 183:231–236.
  • MARSDEN AFA, WILKINSON B, CORTES J, DUNSTER NJ, STAUNTON J, LEADLAY PF: Engineering broader specificity into an antibiotic-producing polyketide synthase. Science i (1998) 279:199–202.
  • PACEY MS, DIRLAM JP, GELDART RW et al.: i Novel erythromycins from a recombinant Saccharopolyspora erythraea i strain NRRL2338 pIG1. I. Fermentation, isolation and biological activity. Antibiot. i (1998) 51:1029–1034.
  • CHUCK JA, MCPHERSON M, HUANG H, JACOBSEN JR, KHOSLA C, CANE DE: Molecular recognition of diketide substrates by a P-ketoacyl-acyl carrier protein synthase domain within a bimodular polyketide synthase. Chem. Biol i (1997) 4:757–766.
  • WEISSMAN KJ, BYCROFT M, CUTTER AL et al: i Evaluating precursor-directed biosynthesis towards novel erythromycins through M vitro i studies on a bimodular polyketide synthase. Chem. Biol i (1998) 5:743–754.
  • LONG PF, WILKINSON CJ, BISANG CP,et al: i Engineering specificity of starter unit selection by the erythromycin-producing polyketide synthase. Mol Microbia i (2002) 43:1215–1225.
  • LEADLAY PF, STAUNTON J, OLIYNYK M et al.: i Engineering of complex polyketide biosynthesis. Insights from sequencing of the monensin biosynthetic gene cluster. Ind. Microbia Biotechnol i (2001) 27:360–367.
  • ROWE CJ, CORTES J, GAISSERS, STAUNTON J, LEADLAY PF: Construction of new vectors for high-level expression in actinomycetes. Gene i (1998) 216:215–223.
  • LIU H, REYNOLDS KA: Precursor supply for polyketide biosynthesis: the role of crotonyl-CoA reductase. Metab. Eng. i (2001) 3:40–48.
  • LIU L, THAMCHAIPENET A, FU H, BETLACH M, ASHLEY G: Biosynthesis of 2-nor-6-deoxyerythronolide B by rationally designed domain substitution. I Am. Chem. Soc. i (1997) 119:10553–10554.
  • STASSI DL, KAKAVAS SJ, REYNOLDS KA et al.: i Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering. Proc. Natl. Acad. ScL USA i (1998) 95:7305–7309.
  • RUAN X, PEREDA A, STASSI DL et al.: i Acyltransferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives. Bacteria i (1997) 179:6416–6425.
  • WU K, CHUNG L, REVILL WP, KATZ L, REEVES CD: The FK520 gene cluster of Streptomyces hygroscopicus i var. ascomyceticus i (ATCC-14891) contains genes for biosynthesis of unusual polyketide extender units. Gene i (2000) 251:81–90.
  • REEVES CD, CHUNG LM, LIU Y et al: i A new substrate specificity for acyl transferase domains of the ascomycin polyketide synthase in Streptomyces hygroscopkus. I Biol. Chem. i (2002) 277:9155–9159.
  • REVILL WP, VODAJ, REEVES CR et al: i Genetically engineered analogs of ascomycin for nerve regeneration. Pharmaca Exp. Ther i (2002) 3:1278–1285.
  • KATO Y, BAI L, XUE Q, REVILL WP, YU TW, FLOSS HG: Functional expression of genes involved in the biosynthesis of the novel polyketide chain extension unit, methoxymalonyl-acyl carrier protein, and engineered biosynthesis of 2-desmethy1-2-methoxy-6-deoxyerythronolide B. I Am. Chem. Soc. i (2002) 124:5268–5269.
  • SCHWECKE T, APARICIO JF, MOLNAR I et al: i The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. Proc. Natl. Acad. ScL USA i (1995) 92:7839–7843.
  • MOTAMEDI H, CAI SJ, SHAFIEE A, ELLISTON KO: Structural organization of a multifunctional polyketide synthase involved in the biosynthesis of the macrolide immunosuppressant FK506. Eur: i Biochem. i (1997) 244:74–80.
  • MOTAMEDI H, SHAFIEE A: The biosynthetic gene cluster for the macrolactone ring of the immunosuppressant FK506. Eur: Biochem. i (1998) 256:528–534.
  • BEDFORD D, JACOBSEN JR, LUO GL, CANE DE, KHOSLA C: A functional chimeric modular polyketide synthase generated via domain replacement. Chem. Biol. i (1996) 3:827–831.
  • MCDANIEL R, KAO CM, FU H et al.: i Gain-of-function mutagenesis of a modular polyketide synthase. j Am. Chem. Soc i (1997) 119:4309–4310.
  • KAO CM, MCPHERSON M, MCDANIEL RN, FU H, CANE DE, KHOSLA C: Gain of function mutagenesis of the erythromycin polyketide synthase. 2. Engineered biosynthesis of eight-membered ring tetraketide lactone. Am. Chem. Soc. i (1997) 119:11339–11340.
  • MCDANIEL R, THAMCHAIPENET A, GUSTAFSSON C et al: i Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel 'unnatural' natural products. Proc. Natl. Acad. Sci. USA i (1999) 96:1846–1851.
  • GAISSER S, KELLENBERGER L, KAJA AL et al.: i Direct production of ivermectin-like drugs after domain exchange in the avermectin polyketide synthase of Streptomyces avermitilis ATCC-31272. Org. Biomol. Chem. i (2003) 1:2840–2847.
  • STUTZMAN-ENGWALL K, CONLON S, FEDECHKO R et al: i Engineering the aveC i gene to enhance the ratio of doramectin to its CHC-B2 analogue produced in Streptomyces Biotechnol Bioeng. i (2003) 82:359–69.
  • REEVES CD, MURLI S, ASHLEY GW, PIAGENTINI M, HUTCHINSON CR, MCDANIEL R: Alteration of the substrate specificity of a modular polyketide synthase acyltransferase domain through site-specific mutations. Biochemistry (2001) i 40:15464–15470.
  • DEL VECCHIO F, PETKOVIC H, KENDREW SG et al.: i Active-site residue, domain and module swaps in modular polyketide synthases. 1 had. Microbia Biotechnol i (2003) 30:489–494.
  • LAU J, FU H, CANE DE, KHOSLA C: Dissecting the role of acyltransferase domains of modular polyketide synthases in the choice and stereochemical fate of extender units. Biochemistry (1999) i 38:1643-1651.
  • REID R, PIAGENTINI M, RODRIGUEZ E et al.: i A model of structure and catalysis for ketoreductase domains in modular polyketide synthases. Biochemistry i (2003) 42:72–79.
  • CAFFREY P: Conserved amino acid residues correlating with ketoreductase stereospecificity in modular polyketide synthases. Chembiochem i (2003) 4:654–657.
  • XUE Q, ASHLEY G, HUTCHINSON CR, SANTI DV: A multiplasmid approach to preparing large libraries of polyketides. Proc. Nati Acad. Sci. USA (1999) i 96:11740-11745.
  • ROWE CJ, BOHM IU, THOMAS IP et al.: i Engineering a polyketide with a longer chain by insertion of an extra module into the erythromycin-producing polyketide synthase. Chem. Biol. i (2001) 8:475–485.
  • BECK BJ, YOON YJ, REYNOLDS KA, SHERMAN DH: The hidden steps of domain skipping. Macrolactone ring size determination in the pikromycin modular polyketide synthase. Chem. Biol. i (2002) 9:575–583.
  • THOMAS I, MARTIN CJ, WILKINSON CJ, STAUNTON J, LEADLAY PF: Skipping in a hybrid polyketide synthase: evidence for ACP-to-ACP chain transfer. Chem. Biol i (2002) 9:781–787.
  • RANGANATHAN A, TIMONEY M, BYCROFT M et al.: i Knowledge-based design of bimodular and trimodular polyketide synthases based on domain and module swaps: a route to simple statin analogues. Chem. Biol. i (1999) 6:731–741.
  • GOKHALE RS, TSUJI SY, CANE DE, KHOSLA C: Dissecting and exploiting intermodular communication in polyketide synthases. Science i (1999) 284:482–485.
  • GOKHALE RS, KHOSLA C: Role of linkers in communication between protein modules. Cum Opin. Chem. Biol(2000) i 4:22–27.
  • OMURA S, IKEDA H, ISHIKAWA J et al.: i Genome sequence of an industrial microorganism Streptomyces avermitilIc i deducing the ability of producing secondary metabolites. Proc. Natl. Acad. Sci. USA (2001) i 98:12215–12220.
  • MCDANIEL R, EBERT-KHOSLA S, HOPWOOD DA, KHOSLA C: Engineered biosynthesis of novel polyketides. Science i (1993) 262:1546–1550.
  • KAO CM, KATZ L, KHOSLA C: Engineered biosynthesis of a complete macrolactone in a heterologous host. Science i (1994) 265:509–512.
  • KIESER T, BIBB MJ, BUTTNER MJ, CHATER KF, HOPWOOD DA: In: Practical Streptomyces genetics. i John Innes Foundation, Norwich, UK (2000).
  • MURAKAMI T, HOLT HG, THOMPSON CJ: Thiostrepton-induced gene expression in Streptomyces lividans. Bacteria (1989) i 171:1459–1466.
  • SALAH-BEY K, BLANC B, THOMPSON CJ: Stress-activated expression of a Streptomyces pristinaespiralis i multidrug resistance gene (ptr) in various Streptomyces i spp. and Escherichia colt. Ma. Microbia i (1995) 17:1001–1012.
  • ROBERTS GA, STAUNTON J, LEADLAY PF: Heterologous expression in Escherichia coliof i an intact multienzyme component of the erythromycin-producing polyketide synthase. Eur. Biochem. (1993) i 214:305–311.
  • LAMBALOT RH, GEHRING AM, FLUGEL RS et al.: i A new enzyme superfamily - the phosphopantetheinyl transferases. Chem. Biol. (1996) i 3:923–936.
  • GEHRING AM, LAMBALOT RH, VOGEL KW, DRUECKHAMMER DG, WALSH CT: Ability of Streptomyces i spp. acyl carrier proteins and coenzyme A analogs to serve as substrates M vitro i for E. coil i holo-ACP synthase. Chem. Biol. (1997) i 4:17–24.
  • PFEIFER BA, ADMIRAAL SJ, GRAMAJO H, CANE DE, KHOSLA C: Biosynthesis of complex polyketides in a metabolically engineered strain of E. colt. Science (2001) i 291:1790-1792.
  • HE L, ORR GA, HORWITZ SB: Novelmolecules that interact with microtubules and have functional activity similar to Taxol. Drug Discov. Today i (2001) 6:1153–1164.
  • MOLNAR I, SCHUPP T, ONO Metal: i The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum i So ce90. Chem. Biol i (2000) 7:97–109.
  • JULIEN B, SHAH S, ZIERMANN R, GOLDMAN R, KATZ L, KHOSLA C: Isolation and characterization of the epothilone gene cluster from Sorangium cellulosum. Gene i (2000) 249:153–160.
  • TANG L, SHAH S, CHUNG L, CARNEY J, KATZ L, KHOSLA C, JULIEN B: Cloning and heterologous expression of the epothilone gene cluster. Science i (2000) 287:640–642.
  • JULIEN B, SHAH S: Heterologous expression of epothilone biosynthetic genes in Myxococcus xanthus. Antimicrob. Agents Chemother i (2002) 46:2772–2778.
  • LUA J, FRYKMAN S, REGENTIN R, OU S, TSURUTA H, LICARI P: Optimizing the heterologous production of epothilone D in Myxococcus xanthus. Biotechnol Bioeng. i (2002) 78:280–288.
  • CHOU T-C, ZHANG X-G, HARRIS CR et al: i Desoxyepothilone B is a curative against human tumor xenografts that are refractory to paclitaxel. Proc. Natl. i Acad. Sci. USA i (1998) 95:15798–15802.
  • MADDURI K, KENNEDY J, RIVOLA G et al: i Production of the antitumor drug epirubicin (4'-epidoxorubicin) and its precursor by a genetically engineered strain of Streptomyces peucetMs. Nat. Biotech i (1998) 16:69-74. los. REMSING LL, GONZALEZ AM, NUR-E-ALEM M et al.: i Mithramycin SK, a novel antitumor drug with improved therapeutic index, mithramycin SA, and demycarosyl-mithramycin SK: three new products generated in the mithramycin producer Streptomyces argillaceus i through combinatorial biosynthesis. J. Am. Chem. Soc. i (2003) 125:5745–5753.
  • XUE Y, ZHAO L, LIU HW, SHERMAN DH: A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: i architecture of metabolic diversity. Proc. Nati Acad. Sci.USA i (1998) 95:12111–12116.
  • SWAN DG, RODRIGUEZ AM, VILCHES C, MENDEZ C, SALAS JA: Characterization of a Streptomyces antibioticus i gene encoding a Type I polyketide synthase which has an unusual coding sequence. MoL Gen. Genet. i (1994) 242:358–362.
  • SHAH S, XUE Q, TANG L, CARNEY JR, BETLACH M, MCDANIEL R: Cloning, characterization and heterologous expression of a polyketide synthase and P450 oxidase involved in the biosynthesis of the antibiotic oleandomycin. Antibia i (2000) 53:502–508.
  • VOLCHEGURSKY Y, HU Z, KATZ L, MCDANIEL R: Biosynthesis of the anti-parasitic agent megalomicin: transformation of erythromycin to megalomicin in Saccharopolyspora erythraea. Mol Microbia (2000) 37:752–762.
  • SUWA M, SUGINO H, SASAOKA A et al: i Identification of two polyketide synthase gene clusters on the linear plasmid pSLA2-L in Smeptomyces rochei Gene i (2000) 246:123–131.
  • KAKAVAS SJ, KATZ L, STASSI D: Identification and characterization of the niddamycin polyketide synthase genes from Streptomyces caelestis. Bacteriol. i (1997) 179:7515–7522.
  • WANG YG, HUTCHINSON CR: Cloning of midecamycin biosynthetic genes from Streptomyces mycarofaciens i 1748. Chin. J. Biotechnol i (1989) 5:191–201.
  • ANZAI Y, SAITO N, TANAKA M, KINOSHITA K, KOYAMA Y, KATO F: Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin in Micromonospora griseaubida. FEMS Microbia Lett i (2003) 218:135–141.
  • MOLNAR I, APARICIO JF, HAYDOCK SF et al.: i Organisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: i analysis of genes flanking the polyketide synthase. Gene i (1996) 169:1–7.
  • RASCHER A, HU Z, VISWANATHAN N et al.: i Cloning and characterization of a gene cluster for geldanamycin production in Streptomyces hygroscopicus i NRRL3602. FEMS Microbia Lett. i (2003) 218:223–230.
  • SHEN B, DU L, SANCHEZ C, EDWARDS DJ, CHEN M, MURRELL JM: Cloning and characterization of the bleomycin biosynthetic gene cluster from Streptomyces verticillus i ATCC-15003. J. Nat. Prod i (2002) 65:422–431.
  • CHENG YQ, TANG GL, SHEN B: Identification and localization of the gene cluster encoding biosynthesis of the antitumor macrolactam leinamycin in Streptomyces amoolivaceus i S-140.1 Bacteria i (2002) 184:7013–7024.
  • YU T-W, BAIL, CLADE D et al: i The biosynthetic gene cluster of the maytansinoid antitumor agent ansamitocin from Actinosynnema i pretiosum. Proc. NatL Acad. Sci.USA (2002) 99:7968–7973.
  • AUGUST PR, TANG L, YOON YJ et al: i Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif i biosynthetic gene cluster of Amycolatopsis mediterranei i S-699. Chem. Biol. i (1998) 5:69–79.
  • SCHUPP T, TOUPET C, ENGEL N, GOFF S: Cloning and sequence analysis of the putative rifamycin polyketide synthase gene cluster from Amycolatopsis meditepanei FEMS Microbia. Lett i (1998) 159:201–207.
  • CHEN S, VON BAMBERG D, HALE V et al: i Biosynthesis of ansatrienin (mycotrienin) and naphthomycin. Identification and analysis of two separate biosynthetic gene clusters in Streptomyces collMus i T0-1892. Puri: Biochem. i (1999) 261:98–107.
  • SUN Y, ZHOU X, DONG H et at i A complete gene cluster from Streptomyces nanchangensis i NS-3226 encoding biosynthesis of the polyether ionophore nanchangmycin. Chem. Biol. i (2003) 10:431–441.
  • APARICIO JF, COLINA AJ, CEBALLOS E, MARTIN JF: 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. Bia Chem. i (1999) 274:10133–10139.
  • CAFFREY P, LYNCH S, FLOOD E, FINNAN S, OLIYNYK M: Amphotericin biosynthesis in Streptomyces nodosus. i deductions from analysis of polyketide synthase and late genes. Chem. Biol. i (2001) 8:713–723.
  • BRAUTASET T, SEKUROVA ON, SLETTA H et al: i Biosynthesis of the polyene antifungal antibiotic nystatin in Streptomyces i nourseiATCC-11455: analysis of the gene cluster and deduction of the biosynthetic pathway. Chem. Biol. i (2000) 7:395–403.
  • CAMPELO AB, GIL JA: The candicidin gene cluster from Streptomycesgriseus i IMRU-3570. Microbiology i (2002) 148:51–59.
  • SILAKOWSKI B, SCHAIRER HU, EHRET H et al.: i New lessons for combinatorial biosynthesis from myxobacteria. The myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca i DW-4/3-1.1 Biol. Chem i (1999) 274:37391–37399.
  • SILAKOWSKI B, NORDSIEK G, KUNZE B, BLOCKER H, MULLER R: Novel features in a combined polyketide synthase/non-ribosomal peptide synthetase: the myxalamid biosynthetic gene cluster of the myxobacterium StigmateIla aurantiaca i SGA-15. Chem. Biol. i (2001) 8:59–69.
  • GAITATZIS N, SILAKOWSKI B, KUNZE B et al.: i The biosynthesis of the aromatic myxobacterial electron transport inhibitor stigmatellin is directed by a novel type of modular polyketide synthase. J. Biol. Chem. i (2002) 277:13082–13090.
  • LIGON J, HILLS, BECK Jet at i Characterization of the biosynthetic gene cluster for the antifungal polyketide soraphen A from Sorangium cellulosum i So CE-26. Gene i (2002) 285:257–267.
  • IKEDA H, NONOMIYA T, USAMI M, OHTA T, OMURA S: Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis Proc. Natl. Acad. Sci. USA i (1999) 96:9509–9514.
  • MACNEIL DJ, OCCIJL, GEWAIN KM et al: i A comparison of the genes encoding the polyketide synthesases for avermectin, erythromycin, and nemadectin. In: Industrial i microorganisms: bask and applied molecular genetics i Baltz RH, Hegeman GD, Skatrud PL (Eds), American Society for Microbiology, Washington DC, USA (1993) 245–256.
  • WEITNAUER G, MUHLENWEG A, TREFZER A et al: i Biosynthesis of the orthosomycin antibiotic avilamycin A: deductions from the molecular analysis of the avi biosynthetic gene cluster of Streptornyces viridochromogenes i TU-57 and production of new antibiotics. Chem. Biol. i (2001) 8:569–581.
  • HOSTED TJ, WANG TX, ALEXANDER DC, HORAN AC: Characterization of the biosynthetic gene cluster for the oligosaccharide antibiotic, everninomycin, in Micromonospora carbonacea i var. thicana i ATCC-39149.1 Ind. Microbiol. Biotechnol i (2001) 27:386–92.
  • EL-SAYED AK, HOTHERSALL J, COOPER SM, STEPHENS E, SIMPSON TJ, THOMAS CM: Characterization of the mupirocin biosynthesis gene cluster from Pseudomonas i fluorescensNCIMB-10586. Chem. Biol. i (2003) 10:419–430.
  • KWON HJ, SMITH WC, SCHARON AJ, HVVANG SH, KURTH MJ, SHEN B: C-0 bond formation by polyketide synthases. Science i (2002) 297:1327–1330.
  • HENDRICKSON L, DAVIS CR, ROACH C et al.: i Lovastatin biosynthesis in Aspergillus terreus: i characterization of blocked mutants, enzyme activities and a multifunctional polyketide synthase gene. Chem. Biol i (1999) 6:429–439.
  • CHANG Z, FLATT P, GERWICK W, NGUYEN V, WILLIS C, SHERMAN D: The barbamide biosynthetic gene cluster: a novel marine cyanobacterial system of mixed polyketide synthase (PKS)-non-ribosomal peptide synthetase (NRPS) origin involving an unusual trichloroleucyl starter unit. Gene i (2002) 296:235–247.
  • AHLERT J, SHEPARD E, LOMOVSKAYA N et al: i The calicheamicin gene cluster and its iterative Type I enediyne PKS. Science i (2002) 297:1173–1176.
  • LIU W, CHRISTENSON SD, STANDAGE S, SHEN B: Biosynthesis of the enediyne antitumor antibiotic C-1027. Science i (2002) 297:1170–1173.
  • WALDRON C, MATSUSHIMA P, ROSTECK PR Jr et al.: i Cloning and analysis of the spinosad biosynthetic gene cluster of Saccharopolyspora spinosa. Chem. Biol. i (2001) 8:487–499.
  • DITTMANN E, NEILAN BA, BORNER T: Molecular biology of peptide and polyketide biosynthesis in cyanobacteria. Appl. Microbiol. Biotechnol i (2001) 57:467–473.
  • MOFFITT MC, NEILAN BA: On the presence of peptide synthetase and polyketide synthase genes in the cyanobacterial genus Nodularia. FEMS Microbiol. Lett i (2001) 196:207–214.
  • MOOTZ HD, SCHWARZER D, MARAHIEL MA: Ways of assembling complex natural products on modular nonribosomal peptide synthetases. Chembiochem i (2002) 3:490–504.
  • SCHWARZER D, FINKING R, MARAHIEL MA: Nonribosomal peptides: from genes to products. Nat. Prod. Rep. i (2003) 20:275–287.
  • HOJATI Z, MILNE C, HARVEY B et al: i Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicoloc Chem. Biol. i (2002) 9:1175–1187.
  • WEIST S, BISTER B, PUK O et al.: i Fluorobalimycin - a new chapter in glycopeptide antibiotic research. Angew. Chem. Int. Ed i (2002) 41:3383–3385.
  • STACHELHAUS T, SCHNEIDER A, MARAHIEL MA: Rational design of peptide antibiotics by targeted replacement of bacterial and fungal domains. Science i (1995) 269:69–72.

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