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Bioscience, Biotechnology, and Biochemistry Volume 72, 2008 - Issue 10
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Original Articles

Exploring the Biosynthesis of Natural Products and Their Inherent Suitability for the Rational Design of Desirable Compounds through Genetic Engineering

Kenji WATANABEDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California
Pages 2491-2506 | Published online: 22 May 2014

  • 1) Crawford, J. M., Thomas, P. M., Scheerer, J. R., Vagstad, A. L., Kelleher, N. L., and Townsend, C. A., Deconstruction of iterative multidomain polyketide synthase function. Science, 320, 243–246 (2008).
  • 2) Burzlaff, N. I., Rutledge, P. J., Clifton, I. J., Hensgens, C. M., Pickford, M., Adlington, R. M., Roach, P. L., and Baldwin, J. E., The reaction cycle of isopenicillin N synthase observed by X-ray diffraction. Nature, 401, 721–724 (1999).
  • 3) Valegård, K., van Scheltinga, A. C., Lloyd, M. D., Hara, T., Ramaswamy, S., Perrakis, A., Thompson, A., Lee, H. J., Baldwin, J. E., Schofield, C. J., Hajdu, J., and Andersson, I., Structure of a cephalosporin synthase. Nature, 394, 805–809 (1998).
  • 4) Koepp, A. E., Hezari, M., Zajicek, J., Vogel, B. S., LaFever, R. E., Lewis, N. G., and Croteau, R., Cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene is the committed step of taxol biosynthesis in the Pacific yew. J. Biol. Chem., 270, 8686–8690 (1995).
  • 5) Tang, L., Shah, S., Chung, L., Carney, J., Katz, L., Khosla, C., and Julien, B., Cloning and heterologous expression of the epothilone gene cluster. Science, 287, 640–642 (2000).
  • 6) Kennedy, J., Auclair, K., Kendrew, S. G., Park, C., Vederas, J. C., and Hutchinson, C. R., Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science, 284, 1368–1372 (1999).
  • 7) Auclair, K., Sutherland, A., Kennedy, J., Witter, D. J., Van den Heever, J. P., Hutchinson, C. R., and Vederas, J. C., Lovastatin nonaketide synthase catalyzes an intramolecular Diels-Alder reaction of a substrate analogue. J. Am. Chem. Soc., 122, 11519–11520 (2000).
  • 8) Oikawa, H., Yagi, K., Watanabe, K., Honma, M., and Ichihara, A., Biosynthesis of macrophomic acid: plausible involvement of intermolecular Diels-Alder reaction. Chem. Commun., 97–98 (1997).
  • 9) Oikawa, H., Watanabe, K., Yagi, K., Ohashi, S., Mie, T., Ichihara, A., and Honma, M., Macrophomate synthase: unusual enzyme catalyzing multiple reactions from pyrones to benzoates. Tetrahedron Lett., 40, 6983–6986 (1999).
  • 10) Watanabe, K., Mie, T., Ichihara, A., Oikawa, H., and Honma, M., Reaction mechanism of the macrophomate synthase: experimental evidence on intermediacy of a bicyclic compound. Tetrahedron Lett., 41, 1443–1446 (2000).
  • 11) Watanabe, K., Oikawa, H., Yagi, K., Ohashi, S., Mie, T., Ichihara, A., and Honma, M., Macrophomate synthase: characterization, sequence, and expression in Escherichia coli of the novel enzyme catalyzing unusual multistep transformation from 2-pyrones to benzoates. J. Biochem., 127, 467–473 (2000).
  • 12) Watanabe, K., Mie, T., Ichihara, A., Oikawa, H., and Honma, M., Substrate diversity of macrophomate synthase catalyzing multistep transformation from 2-pyrones to benzoates. Biosci. Biotechnol. Biochem., 64, 530–538 (2000).
  • 13) Watanabe, K., Mie, T., Ichihara, A., Oikawa, H., and Honma, M., Detailed reaction mechanism of macrophomate synthase: extraordinary enzyme catalyzing five-step transformation from 2-pyrones to benzoates. J. Biol. Chem., 275, 38393–38401 (2000).
  • 14) Oikawa, H., Yagi, K., Ohashi, S., Watanabe, K., Mie, T., Ichihara, A., Honma, M., and Kobayashi, K., Potent inhibition of macrophomate synthase by reaction intermediate analogs. Biosci. Biotechnol. Biochem., 64, 2368–2379 (2000).
  • 15) Ose, T., Watanabe, K., Mie, T., Honma, M., Watanabe, H., Yao, M., Oikawa, H., and Tanaka, I., Insight into a natural Diels-Alder reaction from the structure of macrophomate synthase. Nature, 422, 185–189 (2003).
  • 16) Ichihara, A., and Oikawa, H., Diels-Alder type natural products: structures and biosynthesis. Curr. Org. Chem., 2, 365–394 (1998).
  • 17) Ichihara, A., and Oikawa, H., Comprehensive natural products chemistry. In “The Diels-Alder Reaction in Biosynthesis of Polyketide Phytotoxin,” eds. Barton, D., Nakanishi, K., and Meth-Cohn, O., Elsevier, Amsterdam, pp. 367–408 (1999).
  • 18) Oikawa, H., and Tokiwano, T., Enzymatic catalysis of the Diels-Alder reaction in the biosynthesis of natural products. Nat. Prod. Rep., 21, 321–352 (2004).
  • 19) Kieser, T., Bibb, M. J., Buttner, M. J., Chater, K. F., and Hopwood, D. A., “Practical Streptomyces Genetics,” The John Innes Foundation, Norwich (2000).
  • 20) Kao, C. M., Katz, L., and Khosla, C., Engineered biosynthesis of a complete macrolactone in a heterologous host. Science, 265, 509–512 (1994).
  • 21) Desai, R. P., Leaf, T., Woo, E., and Licari, P., Enhanced production of heterologous macrolide aglycones by fed-batch cultivation of Streptomyces coelicolor. J. Ind. Microbiol. Biotechnol., 5, 297–301 (2002).
  • 22) Julia, P., Li, X., Whiting, A., Latif, M., Gibson, T., Silva, C. J., Brain, P., Davies, J., Miao, V., Wrigley, S. K., and Baltz, R. H., Heterologous production of daptomycin in Streptomyces lividans. J. Ind. Microbiol. Biotechnol., 33, 121–128 (2006).
  • 23) Miao, V. M., Gal, C., Nguyen, K., Brian, P., Penn, J., Whiting, A., Steele, J., Kau, D., Martin, S., Ford, R., Gibson, T., Richard, M., and Baltz, H., Genetic engineering in Streptomyces roseosporus to produce hybrid lipopeptide antibiotics. Chem. Biol., 13, 269–276 (2006).
  • 24) Ro, D. K., Paradise, E. M., Ouellet, M., Fisher, K. J., Newman, K. L., Ndungu, J. M., Ho, K. A., Eachus, R. A., Ham, T. S., Kirby, J., Chang, M. C., Withers, S. T., Shiba, Y., Sarpong, R., and Keasling, J. D., Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature, 440, 940–943 (2006).
  • 25) Pfeifer, B. A., Admiraal, S. J., Gramajo, H., Cane, D. E., and Khosla, C., Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli. Science, 291, 1790–1792 (2001).
  • 26) Pfeifer, B. A., Wang, C. C., Walsh, C. T., and Khosla, C., Biosynthesis of yersiniabactin, a complex polyketide-nonribosomal peptide, using Escherichia coli as a heterologous host. Appl. Environ. Microbiol., 69, 6698–6702 (2003).
  • 27) Watanabe, K., Rude, M. A., Walsh, C. T., and Khosla, C., Engineered biosynthesis of an ansamycin polyketide precursor in Escherichia coli. Proc. Natl. Acad. Sci. USA, 100, 9774–9778 (2003).
  • 28) Murli, S., Kennedy, J., Dayem, L. C., Carney, J. R., and Kealey, J. T., Metabolic engineering of Escherichia coli for improved 6-deoxyerythronolide B production. J. Ind. Microbiol. Biotechnol., 30, 500–509 (2003).
  • 29) Lau, J., Tran, C., Licari, P., and Galazzo, J., Development of a high cell-density fed-batch bioprocess for the heterologous production of 6-deoxyerythronolide B in Escherichia coli. J. Biotechnol., 110, 95–103 (2004).
  • 30) Yokoyama, T., Descriptive catalogue of IFO fungus collection V. IFO Res. Commun., 8, 79–89 (1977).
  • 31) Shimizu, S., Sakurai, I., and Yamamoto, Y., Isolation and structure of macommelins, novel metabolites of Macrophoma commelinae. Chem. Pharm. Bull., 31, 3781–3784 (1983).
  • 32) Sakurai, I., Suzuki, H., Shimizu, S., and Yamamoto, Y., Novel biotransformation of a 2-pyrone to a substituted benzoic acid. Chem. Pharm. Bull., 33, 5141–5143 (1985).
  • 33) Sakurai, I., Shimizu, S., and Yamamoto, Y., Studies on metabolites of Macrophoma commelinae. III. Chem. Pharm. Bull., 36, 1328–1335 (1988).
  • 34) Sakurai, I., Miyajima, H., Akiyama, K., Shimizu, S., and Yamamoto, Y., Studies on metabolites of Macrophoma commelinae. IV. Chem. Pharm. Bull., 36, 2003–2011 (1988).
  • 35) Serafimov, J. M., Westfeld, T., Meier, B. H., and Hilvert, D., Trapping and structure elucidation of an intermediate in the macrophomate synthase reaction pathway. J. Am. Chem. Soc., 129, 9580–9581 (2007).
  • 36) Cortes, J., Haydock, S. F., Roberts, G. A., Bevitt, D. J., and Leadlay, P. F., An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature, 348, 176–178 (1990).
  • 37) Donadio, S., Staver, M. J., McAlpine, J. B., Swanson, S. J., and Katz, L., Modular organization of genes required for complex polyketide biosynthesis. Science, 252, 675–679 (1991).
  • 38) Krause, M., and Marahiel, M. A., Organization of the biosynthesis genes for the peptide antibiotic gramicidin S. J. Bacteriol., 170, 4669–4674 (1988).
  • 39) Armstrong, G. A., Alberti, M., Leach, F., and Hearst, J. E., Nucleotide sequence, organization, and nature of the protein products of the carotenoid biosynthesis gene cluster of Rhodobacter capsulatus. Mol. Gen. Genet., 216, 254–268 (1989).
  • 40) Ota, Y., Tamegai, H., Kudo, F., Kuriki, H., Koike-Takeshita, A., Eguchi, T., and Kakinuma, K., Butirosin-biosynthetic gene cluster from Bacillus circulans. J. Antibiotics (Tokyo), 53, 1158–1167 (2000).
  • 41) Tamegai, H., Nango, E., Koike-Takeshita, A., Kudo, F., and Kakinuma, K., Significance of the 20-kDa subunit of heterodimeric 2-deoxy-scyllo-inosose synthase for the biosynthesis of butirosin antibiotics in Bacillus circulans. Biosci. Biotechnol. Biochem., 66, 1538–1545 (2002).
  • 42) Cane, D. E., Walsh, C. T., and Khosla, C., Harnessing the biosynthetic code: combinations, permutations, and mutations. Science, 282, 63–68 (1998).
  • 43) Walsh, C. T., Polyketide and nonribosomal peptide antibiotics: modularity and versatility. Science, 303, 1805–1810 (2004).
  • 44) Hutchinson, C. R., Polyketide and non-ribosomal peptide synthases: falling together by coming apart. Proc. Natl. Acad. Sci. USA, 100, 3010–3012 (2003).
  • 45) Watanabe, K., Hotta, K., Praseuth, A. P., Koketsu, K., Migita, A., Boddy, C. N., Wang, C. C. C., Oguri, H., and Oikawa, H., Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli. Nat. Chem. Biol., 2, 423–428 (2006).
  • 46) Tsuji, S. Y., Cane, D. E., and Khosla, C., Selective protein-protein interactions direct channeling of intermediates between polyketide synthase modules. Biochemistry, 40, 2326–2331 (2001).
  • 47) Steinerova, N., Lipavska, H., Stajner, K., Caslavska, J., Blumauerova, M., Cudlin, J., and Vanek, Z., Production of quinomycin A in Streptomyces lasaliensis. Folia Microbiol. (Praha), 32, 1–5 (1987).
  • 48) Romero, F., Espliego, F., Pérez, B. J., García de Quesada, T., Grávalos, D., de la Calle, F., and Fernández-Puentes, J. L., Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activities. J. Antibiotics (Tokyo), 50, 734–737 (1997).
  • 49) Takusagawa, F., The role of the cyclic depsipeptide rings in antibiotics. J. Antibiotics (Tokyo), 38, 1596–1604 (1985).
  • 50) Waring, M., and Makoff, A., Breakdown of pulse-labeled ribonucleic acid and polysomes in Bacillus megaterium: actions of streptolydigin, echinomycin, and triostins. Mol. Pharmacol., 10, 214–224 (1974).
  • 51) Boger, D. L., Ichikawa, S., Tse, W. C., Hedrick, M. P., and Jin, Q., Total syntheses of thiocoraline and BE-22179 and assessment of their DNA binding and biological properties. J. Am. Chem. Soc., 123, 561–568 (2001).
  • 52) Ughetto, G., Wang, A. H., Quigley, G. J., van der Marel, G. A., van Boom, J. H., and Rich, A., A comparison of the structure of echinomycin and triostin A complexed to a DNA fragment. Nucleic Acids Res., 13, 2305–2323 (1985).
  • 53) Searle, M. S., Hall, J. G., Denny, W. A., and Wakelin, L. P., Interaction of the antitumour antibiotic luzopeptin with the hexanucleotide duplex d(5′-GCATGC)2: one-dimensional and two-dimensional n.m.r. studies. Biochem. J., 259, 433–441 (1989).
  • 54) Chen, H., and Patel, D. J., Solution structure of a quinomycin bisintercalator-DNA complex. J. Mol. Biol., 246, 164–179 (1995).
  • 55) Rance, M. J., Ruddock, J. C., Pacey, M. S., Cullen, W. P., Huang, L. H., Jefferson, M. T., Whipple, E. B., Maeda, H., and Tone, J., UK-63,052 complex, new quinomycin antibiotics from Streptomyces braegensis subsp. japonicus; taxonomy, fermentation, isolation, characterisation and antimicrobial activity. J. Antibiotics (Tokyo), 42, 206–217 (1989).
  • 56) Kurosawa, K., Takahashi, K., and Tsuda, E., SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. I. Taxonomy, fermentation, isolation and biological activities. J. Antibiotics (Tokyo), 54, 615–621 (2001).
  • 57) Takahashi, K., Koshino, H., Esumi, Y., Tsuda, E., and Kurosawa, K., SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. II. Structure elucidation. J. Antibiotics (Tokyo), 54, 622–627 (2001).
  • 58) Nakaya, M., Oguri, H., Takahashi, K., Fukushi, E., Watanabe, K., and Oikawa, H., Relative and absolute configuration of antitumor agent SW-163D. Biosci. Biotechnol. Biochem., 71, 2969–2977 (2007).
  • 59) Fox, K. R., Footprinting studies of the interaction of quinomycin antibiotic UK63052 with DNA: comparison with echinomycin. J. Antibiotics (Tokyo), 43, 1307–1315 (1990).
  • 60) Lee, J. S., and Waring, M. J., Bifunctional intercalation and sequence specificity in the binding of quinomycin and triostin antibiotics to deoxyribonucleic acid. Biochem. J., 173, 115–128 (1978).
  • 61) Reid, D. G., Doddrell, D. M., Williams, D. H., and Fox, K. R., A 15N nuclear magnetic resonance study of the biosynthesis of quinoxaline antibiotics. Biochim. Biophys. Acta, 798, 111–114 (1984).
  • 62) Koketsu, K., Oguri, H., Watanabe, K., and Oikawa, H., Identification and stereochemical assignment of the β-hydroxytryptophan intermediate in the echinomycin biosynthetic pathway. Org. Lett., 8, 4719–4722 (2006).
  • 63) Schmoock, G., Pfenning, F., Jewiarz, J., Schlumbohm, W., Laubinger, W., Schauwecker, F., and Keller, U., Functional cross-talk between fatty acid synthesis and nonribosomal peptide synthesis in quinoxaline antibiotic-producing streptomycetes. J. Biol. Chem., 280, 4339–4349 (2005).
  • 64) Cornish, A., Waring, M. J., and Nolan, R. D., Conversion of triostins to quinomycins by protoplasts of Streptomyces echinatus. J. Antibiotics (Tokyo), 36, 1664–1670 (1983).
  • 65) Lomovskaya, N., Hong, S. K., Kim, S. U., Fonstein, L., Furuya, K., and Hutchinson, C. R., The Streptomyces peucetius drrC gene encodes a UvrA-like protein involved in daunorubicin resistance and production. J. Bacteriol., 178, 3238–3245 (1996).
  • 66) Furuya, K., and Hutchinson, C. R., The DrrC protein of Streptomyces peucetius, a UvrA-like protein, is a DNA-binding protein whose gene is induced by daunorubicin. FEMS Microbiol. Lett., 168, 243–249 (1998).
  • 67) Hildebrand, M., Waggoner, L. E., Liu, H., Sudek, S., Allen, S., Anderson, C., Sherman, D. H., and Haygood, M., bryA: an unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina. Chem. Biol., 11, 1543–1552 (2004).
  • 68) Sudek, S., Lopanik, N. B., Waggoner, L. E., Hildebrand, M., Anderson, C., Liu, H., Patel, A., Sherman, D. H., and Haygood, M. G., Identification of the putative bryostatin polyketide synthase gene cluster from “Candidatus Endobugula sertula,” the uncultivated microbial symbiont of the marine bryozoan Bugula neritina. J. Nat. Prod., 70, 67–74 (2007).
  • 69) Li, L., Deng, W., Song, J., Ding, W., Zhao, Q. F., Peng, C., Song, W. W., Tang, G. L., and Liu, W., Characterization of the saframycin A gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner. J. Bacteriol., 190, 251–263 (2008).
  • 70) Velasco, A., Acebo, P., Gomez, A., Schleissner, C., Rodríguez, P., Aparicio, T., Conde, S., Muñoz, R., de la Calle, F., Garcia, J. L., and Sánchez-Puelles, J. M., Molecular characterization of the safracin biosynthetic pathway from Pseudomonas fluorescens A2–2: designing new cytotoxic compounds. Mol. Microbiol., 56, 144–154 (2005).
  • 71) Watanabe, K., Praseuth, A. P., and Wang, C. C., A comprehensive and engaging overview of the type III family of polyketide synthases. Curr. Opin. Chem. Biol., 11, 279–286 (2007).
  • 72) Watanabe, K., and Oikawa, H., Robust platform for de novo production of heterologous polyketides and nonribosomal peptides in Escherichia coli. Org. Biomol. Chem., 21, 593–602 (2007).
  • 73) Wildung, M. R., and Croteau, R., A cDNA clone for taxadiene synthase, the diterpene cyclase that catalyzes the committed step of taxol biosynthesis. J. Biol. Chem., 271, 9201–9204 (1996).
  • 74) Jennewein, S., Rithner, C. D., Williams, R. M., and Croteau, R. B., Taxol biosynthesis: taxane 13 alpha-hydroxylase is a cytochrome P450-dependent monooxygenase. Proc. Natl. Acad. Sci. USA, 98, 13595–13600 (2001).

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