Natural Products Version 2.0: Connecting Genes to Molecules

Natural products as sources of new drugs over the last 25 years

Newman, D. J., & Cragg, G. M. (2007) · Journal of Natural Products · doi:10.1021/np068054v · Cited by 5,517

The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease

Lamb, J., Crawford, E. D., Peck, D., Modell, J. W., Blat, I. C., Wrobel, M. J., Lerner, J., Brunet, J.-P., Subramanian, A., Ross, K. N., et al. (2006) · Science · doi:10.1126/science.1132939 · Cited by 5,257

Next-generation DNA sequencing

Shendure, J., & Ji, H. (2008) · Nature Biotechnology · doi:10.1038/nbt1486 · Cited by 4,509

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2)

Bentley, S. D., Chater, K. F., Cerdeño-Tárraga, A.-M., Challis, G. L., Thomson, N. R., James, K. D., Harris, D. E., Quail, M. A., Kieser, H., Harper, D., et al. (2002) · Nature · doi:10.1038/417141a · Cited by 3,233

Biochemistry & molecular biology of plants

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Production of the antimalarial drug precursor artemisinic acid in engineered yeast

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., et al. (2006) · Nature · doi:10.1038/nature04640 · Cited by 2,805

Dioxygen Activation at Mononuclear Nonheme Iron Active Sites: Enzymes, Models, and Intermediates

Costas, M., Mehn, M. P., Jensen, M. P., & Que, L. (2004) · Chemical Reviews · doi:10.1021/cr020628n · Cited by 2,472

Staurosporine, a potent inhibitor of phospholipidCa++dependent protein kinase

Tamaoki, T., Nomoto, H., Takahashi, I., Kato, Y., Morimoto, M., & Tomita, F. (1986) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(86)90008-2 · Cited by 2,452

Glycosyltransferases: Structures, Functions, and Mechanisms

Lairson, L. L., Henrissat, B., Davies, G. J., & Withers, S. G. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.061005.092322 · Cited by 2,079

Drug Discovery and Natural Products: End of an Era or an Endless Frontier?

Li, J. W.-H., & Vederas, J. C. (2009) · Science · doi:10.1126/science.1168243 · Cited by 2,052

Plants as a source of anti-cancer agents

Cragg, G. M., & Newman, D. J. (2005) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2005.05.011 · Cited by 2,034

Antibiotics for Emerging Pathogens

Fischbach, M. A., & Walsh, C. T. (2009) · Science · doi:10.1126/science.1176667 · Cited by 1,777

Plants as source of drugs

Rates, S. M. K. (2001) · Toxicon · doi:10.1016/s0041-0101(00)00154-9 · Cited by 1,490

Assembly-Line Enzymology for Polyketide and Nonribosomal Peptide Antibiotics: Logic, Machinery, and Mechanisms

Fischbach, M. A., & Walsh, C. T. (2006) · Chemical Reviews · doi:10.1021/cr0503097 · Cited by 1,464

Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug

Capdeville, R., Buchdunger, E., Zimmermann, J., & Matter, A. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd839 · Cited by 1,389

The Biosynthetic Logic of Polyketide Diversity

Hertweck, C. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200806121 · Cited by 1,346

A Predictably Selective Aliphatic C–H Oxidation Reaction for Complex Molecule Synthesis

Chen, M. S., & White, M. C. (2007) · Science · doi:10.1126/science.1148597 · Cited by 1,291

Pyrrole, pyrrolidine, pyridine, piperidine and tropane alkaloids (1998 to 1999)

O’Hagan, D. (2000) · Natural Product Reports · doi:10.1039/a707613d · Cited by 1,249

Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis

Ikeda, H., Ishikawa, J., Hanamoto, A., Shinose, M., Kikuchi, H., Shiba, T., Sakaki, Y., Hattori, M., & Ōmura, S. (2003) · Nature Biotechnology · doi:10.1038/nbt820 · Cited by 1,241

The specificity-conferring code of adenylation domains in nonribosomal peptide synthetases

Stachelhaus, T., Mootz, H. D., & Marahiel, M. A. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)80082-9 · Cited by 1,237

Modular Peptide Synthetases Involved in Nonribosomal Peptide Synthesis

Marahiel, M. A., Stachelhaus, T., & Mootz, H. D. (1997) · Chemical Reviews · doi:10.1021/cr960029e · Cited by 1,126

Salinosporamide A: A Highly Cytotoxic Proteasome Inhibitor from a Novel Microbial Source, a Marine Bacterium of the New Genus Salinospora

Feling, R. H., Buchanan, G. O., Mincer, T. J., Kauffman, C. A., Jensen, P. R., & Fenical, W. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200390115 · Cited by 1,057

Bacterially Speaking

Bassler, B. L., & Losick, R. (2006) · Cell · doi:10.1016/j.cell.2006.04.001 · Cited by 983

Dysregulation of the TSC-mTOR pathway in human disease

Inoki, K., Corradetti, M. N., & Guan, K.-L. (2005) · Nature Genetics · doi:10.1038/ng1494 · Cited by 972

Property Distributions: Differences between Drugs, Natural Products, and Molecules from Combinatorial Chemistry

Feher, M., & Schmidt, J. M. (2003) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci0200467 · Cited by 927

How many antibiotics are produced by the genus Streptomyces ?

Watve, M., Tickoo, R., Jog, M., & Bhole, B. (2001) · Archives of Microbiology · doi:10.1007/s002030100345 · Cited by 923

Modular Organization of Genes Required for Complex Polyketide Biosynthesis

Donadio, S., Staver, M. J., McAlpine, J. B., Swanson, S. J., & Katz, L. (1991) · Science · doi:10.1126/science.2024119 · Cited by 898

Cytochrome P450

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Regulation of secondary metabolism in streptomycetes

Bibb, M. J. (2005) · Current Opinion in Microbiology · doi:10.1016/j.mib.2005.02.016 · Cited by 821

Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains

Challis, G. L., Ravel, J., & Townsend, C. A. (2000) · Chemistry & Biology · doi:10.1016/s1074-5521(00)00091-0 · Cited by 806

Genome sequence of an industrial microorganism Streptomyces avermitilis : Deducing the ability of producing secondary metabolites

Ōmura, S., Ikeda, H., Ishikawa, J., Hanamoto, A., Takahashi, C., Shinose, M., Takahashi, Y., Horikawa, H., Nakazawa, H., Osonoe, T., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211433198 · Cited by 801

Stereoselective Bimolecular Phenoxy Radical Coupling by an Auxiliary (Dirigent) Protein Without an Active Center

Davin, L. B., Wang, H.-B., Crowell, A. L., Bedgar, D. L., Martin, D. M., Sarkanen, S., & Lewis, N. G. (1997) · Science · doi:10.1126/science.275.5298.362 · Cited by 755

Biosynthesis of Complex Polyketides in a Metabolically Engineered Strain of E. coli

Pfeifer, B. A., Admiraal, S. J., Gramajo, H., Cane, D. E., & Khosla, C. (2001) · Science · doi:10.1126/science.1058092 · Cited by 750

Pathogenic fungus harbours endosymbiotic bacteria for toxin production

Partida-Martinez, L. P., & Hertweck, C. (2005) · Nature · doi:10.1038/nature03997 · Cited by 677

Antibiotics: Actions, Origins, Resistance

Walsh, C. T. (2003) · Medical Entomology and Zoology · Cited by 675

Asymmetric Catalysis Mediated by Synthetic Peptides

Davie, E. A. C., Mennen, S. M., Xu, Y., & Miller, S. J. (2007) · Chemical Reviews · doi:10.1021/cr068377w · Cited by 652

Antibiotics: Actions, Origins, Resistance

Walsh, C. (2003) · Wiley eBooks · doi:10.1128/9781555817886 · Cited by 633

An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea

Cortes, J., Haydock, S. F., Roberts, G. A., Bevitt, D. J., & Leadlay, P. F. (1990) · Nature · doi:10.1038/348176a0 · Cited by 624

Thiopeptide Antibiotics

Bagley, M. C., Dale, J. W., Merritt, E. A., & Xiong, X. (2005) · Chemical Reviews · doi:10.1021/cr0300441 · Cited by 612

A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles

Piel, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222481399 · Cited by 609

Synthesis at the molecular frontier

Wender, P. A., & Miller, B. L. (2009) · Nature · doi:10.1038/460197a · Cited by 579

Metabolites from symbiotic bacteria

Piel, J. (2009) · Nat. Prod. Rep. · doi:10.1039/b703499g · Cited by 577

Triggering cryptic natural product biosynthesis in microorganisms

Scherlach, K., & Hertweck, C. (2009) · Organic & Biomolecular Chemistry · doi:10.1039/b821578b · Cited by 574

Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni , the cyanobacterial symbiont of Lissoclinum patella

Schmidt, E. W., Nelson, J. T., Rasko, D. A., Sudek, S., Eisen, J. A., Haygood, M. G., & Ravel, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501424102 · Cited by 567

Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms

Shen, B. (2003) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(03)00020-6 · Cited by 565

Genome Sequence of the Streptomycin-Producing Microorganism Streptomyces griseus IFO 13350

Ohnishi, Y., Ishikawa, J., Hara, H., Suzuki, H., Ikenoya, M., Ikeda, H., Yamashita, A., Hattori, M., & Horinouchi, S. (2008) · Journal of Bacteriology · doi:10.1128/jb.00204-08 · Cited by 563

Regulation of Secondary Metabolism in Filamentous Fungi

Yu, J.-H., & Keller, N. (2005) · Annual Review of Phytopathology · doi:10.1146/annurev.phyto.43.040204.140214 · Cited by 562

Rhizobium symbiosis: nod factors in perspective.

Long, S. R. (1996) · The Plant Cell · doi:10.1105/tpc.8.10.1885 · Cited by 553

The role of carbohydrates in biologically active natural products

Weymouth-Wilson, A. C. (1997) · Natural Product Reports · doi:10.1039/np9971400099 · Cited by 553

Strategies for discovering drugs from previously unexplored natural products

Harvey, A. (2000) · Drug Discovery Today · doi:10.1016/s1359-6446(00)01511-7 · Cited by 542

Automated Synthesis of Peptides: Solid-phase peptide synthesis, a simple and rapid synthetic method, has now been automated.

Merrifield, R. B. (1965) · Science · doi:10.1126/science.150.3693.178 · Cited by 540

Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica

Udwary, D. W., Zeigler, L., Asolkar, R. N., Singan, V., Lapidus, A., Fenical, W., Jensen, P. R., & Moore, B. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700962104 · Cited by 536

Flavoenzymes: diverse catalysts with recurrent features

Fraaije, M. W., & Mattevi, A. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01533-9 · Cited by 519

Bacterial Protection of Beetle-Fungus Mutualism

Scott, J. J., Oh, D.-C., Yuceer, M. C., Klepzig, K. D., Clardy, J., & Currie, C. R. (2008) · Science · doi:10.1126/science.1160423 · Cited by 478

Biosynthesis of Plant Isoprenoids: Perspectives for Microbial Engineering

Kirby, J., & Keasling, J. D. (2009) · Annual Review of Plant Biology · doi:10.1146/annurev.arplant.043008.091955 · Cited by 478

RECENT ADVANCES IN UNDERSTANDING LIGNIN BIOSYNTHESIS

Whetten, R. W., MacKay, J. J., & Sederoff, R. R. (1998) · Annual Review of Plant Physiology and Plant Molecular Biology · doi:10.1146/annurev.arplant.49.1.585 · Cited by 477

Metabolomics Reviewed: A New “Omics” Platform Technology for Systems Biology and Implications for Natural Products Research

Rochfort, S. (2005) · Journal of Natural Products · doi:10.1021/np050255w · Cited by 465

Evolution of sensory complexity recorded in a myxobacterial genome

Goldman, B. S., Nierman, W. C., Kaiser, D., Slater, S. C., Durkin, A. S., Eisen, J. A., Ronning, C. M., Barbazuk, W. B., Blanchard, M., Field, C., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607335103 · Cited by 450

The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin.

Schwecke, T., Aparicio, J. F., Molnár, I., König, A., Khaw, L. E., Haydock, S. F., Oliynyk, M., Caffrey, P., Cortés, J., & Lester, J. B. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.17.7839 · Cited by 445

Natural‐Product Sugar Biosynthesis and Enzymatic Glycodiversification

Thibodeaux, C. J., Melançon, C. E., & Liu, H. (2008) · Angewandte Chemie International Edition · doi:10.1002/anie.200801204 · Cited by 444

Designed divergent evolution of enzyme function

Yoshikuni, Y., Ferrin, T. E., & Keasling, J. D. (2006) · Nature · doi:10.1038/nature04607 · Cited by 438

Structure of isopenicillinN synthase complexed with substrate and the mechanism ofpenicillin formation

Roach, P. L., Clifton, I. J., Hensgens, C. M. H., Shibata, N., Schofield, C. J., Hajdu, J., & Baldwin, J. E. (1997) · Nature · doi:10.1038/42990 · Cited by 437

Structures of MLSBK Antibiotics Bound to Mutated Large Ribosomal Subunits Provide a Structural Explanation for Resistance

Tu, D., Blaha, G., Moore, P. B., & Steitz, T. A. (2005) · Cell · doi:10.1016/j.cell.2005.02.005 · Cited by 433

Complete genome sequence of the myxobacterium Sorangium cellulosum

Schneiker, S., Perlova, O., Kaiser, O., Gerth, K., Alici, A., Altmeyer, M. O., Bartels, D., Bekel, T., Beyer, S., Bode, E., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1354 · Cited by 425

Cloning and Heterologous Expression of the Epothilone Gene Cluster

Tang, L., Shah, S., Chung, L., Carney, J., Katz, L., Khosla, C., & Julien, B. (2000) · Science · doi:10.1126/science.287.5453.640 · Cited by 424

Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338

Oliynyk, M., Samborskyy, M., Lester, J. B., Mironenko, T., Scott, N., Dickens, S., Haydock, S. F., & Leadlay, P. F. (2007) · Nature Biotechnology · doi:10.1038/nbt1297 · Cited by 402

Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection

Nguyen, T., Ishida, K., Jenke-Kodama, H., Dittmann, E., Gurgui, C., Hochmuth, T., Taudien, S., Platzer, M., Hertweck, C., & Piel, J. (2008) · Nature Biotechnology · doi:10.1038/nbt1379 · Cited by 390

Biosynthetic Intermediate Analysis and Functional Homology Reveal a Saxitoxin Gene Cluster in Cyanobacteria

Kellmann, R., Mihali, T. K., Jeon, Y. J., Pickford, R., Pomati, F., & Neilan, B. A. (2008) · Applied and Environmental Microbiology · doi:10.1128/aem.00353-08 · Cited by 390

Structure of cytochrome P450eryF involved in erythromycin biosynthesis

Cupp-Vickery, J. R., & Poulos, T. L. (1995) · Nature Structural & Molecular Biology · doi:10.1038/nsb0295-144 · Cited by 371

High-Level Production of Amorpha-4,11-Diene, a Precursor of the Antimalarial Agent Artemisinin, in Escherichia coli

Tsuruta, H., Paddon, C. J., Eng, D., Lenihan, J. R., Horning, T., Anthony, L. C., Regentin, R., Keasling, J. D., Renninger, N. S., & Newman, J. D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004489 · Cited by 363

Vancomycin Assembly: Nature's Way

Hubbard, B. K., & Walsh, C. T. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200390202 · Cited by 356

Diversity, regulation, and evolution of the gibberellin biosynthetic pathway in fungi compared to plants and bacteria

Bömke, C., & Tudzynski, B. (2009) · Phytochemistry · doi:10.1016/j.phytochem.2009.05.020 · Cited by 340

Structure of a cephalosporin synthase

Valegård, K., van Scheltinga, A. C. T., Lloyd, M. D., Hara, T., Ramaswamy, S., Perrakis, A., Thompson, A., Lee, H.-J., Baldwin, J. E., Schofield, C. J., et al. (1998) · Nature · doi:10.1038/29575 · Cited by 337

Biosynthesis of polyketide synthase extender units

Chan, Y. A., Podevels, A. M., Kevany, B. M., & Thomas, M. G. (2009) · Nat. Prod. Rep. · doi:10.1039/b801658p · Cited by 337

Crystal Structure of the Termination Module of a Nonribosomal Peptide Synthetase

Tanovic, A., Samel, S. A., Essen, L.-O., & Marahiel, M. A. (2008) · Science · doi:10.1126/science.1159850 · Cited by 337

Cryptic chlorination by a non-haem iron enzyme during cyclopropyl amino acid biosynthesis

Vaillancourt, F. H., Yeh, E., Vosburg, D. A., O'Connor, S. E., & Walsh, C. T. (2005) · Nature · doi:10.1038/nature03797 · Cited by 322

A Widely Distributed Bacterial Pathway for Siderophore Biosynthesis Independent of Nonribosomal Peptide Synthetases

Challis, G. L. (2005) · ChemBioChem · doi:10.1002/cbic.200400283 · Cited by 321

Unearthing the roots of the terpenome

Christianson, D. W. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2007.12.008 · Cited by 318

Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics

Donadio, S., Monciardini, P., & Sosio, M. (2007) · Natural Product Reports · doi:10.1039/b514050c · Cited by 309

Abyssomicin C—A Polycyclic Antibiotic from a Marine Verrucosispora Strain as an Inhibitor of the p ‐Aminobenzoic Acid/Tetrahydrofolate Biosynthesis Pathway

Bister, B., Bischoff, D., Ströbele, M., Riedlinger, J., Reicke, A., Wolter, F., Bull, A. T., Zähner, H., Fiedler, H., & Süssmuth, R. D. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200353160 · Cited by 309

Translational Regulation via L11: Molecular Switches on the Ribosome Turned On and Off by Thiostrepton and Micrococcin

Harms, J. M., Wilson, D. N., Schluenzen, F., Connell, S. R., Stachelhaus, T., Zaborowska, Z., Spahn, C. M. T., & Fucini, P. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.01.009 · Cited by 302

Biosynthesis and attachment of novel bacterial polyketide synthase starter units

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Tailoring enzymes that modify nonribosomal peptides during and after chain elongation on NRPS assembly lines

Walsh, C. T., Chen, H., Keating, T. A., Hubbard, B. K., Losey, H. C., Luo, L., Marshall, C. G., Miller, D. A., & Patel, H. M. (2001) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(00)00235-0 · Cited by 301

The Calicheamicin Gene Cluster and Its Iterative Type I Enediyne PKS

Ahlert, J., Shepard, E., Lomovskaya, N., Zazopoulos, E., Staffa, A., Bachmann, B. O., Huang, K., Fonstein, L., Czisny, A., Whitwam, R. E., et al. (2002) · Science · doi:10.1126/science.1072105 · Cited by 292

Vancomycin Assembly: Nature′s Way

Hubbard, B. K., & Walsh, C. T. (2003) · ChemInform · doi:10.1002/chin.200322284 · Cited by 290

The parallel and convergent universes of polyketide synthases and nonribosomal peptide synthetases

Cane, D. E., & Walsh, C. T. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(00)80001-0 · Cited by 287

The Pseudomonas phytotoxin coronatine mimics octadecanoid signalling molecules of higher plants

Weiler, E. W., Kutchan, T. M., Gorba, T., Brodschelm, W., Niesel, U., & Bublitz, F. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00411-0 · Cited by 283

The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase

Du, L., Sánchez, C., Chen, M., Edwards, D. J., & Shen, B. (2000) · Chemistry & Biology · doi:10.1016/s1074-5521(00)00011-9 · Cited by 282

Biosynthesis of the Enediyne Antitumor Antibiotic C-1027

Liu, W., Christenson, S. D., Standage, S., & Shen, B. (2002) · Science · doi:10.1126/science.1072110 · Cited by 281

The 2.7-Å crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase

Tang, Y., Kim, C., Mathews, I. I., Cane, D. E., & Khosla, C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601924103 · Cited by 280

Structure and Biosynthesis of Heat-Stable Antifungal Factor (HSAF), a Broad-Spectrum Antimycotic with a Novel Mode of Action

Yu, F., Zaleta-Rivera, K., Zhu, X., Huffman, J., Millet, J. C., Harris, S. D., Yuen, G., Li, X.-C., & Du, L. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00931-06 · Cited by 265

Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians

Donia, M. S., Hathaway, B. J., Sudek, S., Haygood, M. G., Rosovitz, M. J., Ravel, J., & Schmidt, E. W. (2006) · Nature Chemical Biology · doi:10.1038/nchembio829 · Cited by 261

The FK520 gene cluster of Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units

Wu, K., Chung, L., Revill, W. P., Katz, L., & Reeves, C. D. (2000) · Gene · doi:10.1016/s0378-1119(00)00171-2 · Cited by 259

Taxol: biosynthesis, molecular genetics, and biotechnological applications

S., J., & R., C. (2001) · Applied Microbiology and Biotechnology · doi:10.1007/s002530100757 · Cited by 253

Marcel Faber Roundtable: Is our antibiotic pipeline unproductive because of starvation, constipation or lack of inspiration?

Baltz, R. H. (2006) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-005-0077-9 · Cited by 246

Fluorescence Resonance Energy Transfer as a Probe for G-Quartet Formation by a Telomeric Repeat

Mergny, J., & Maurizot, J. (2001) · ChemBioChem · doi:10.1002/1439-7633(20010202)2:2<99::aid-cbic99>3.0.co;2-3 · Cited by 245

Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: Analysis of the enzymatic domains in the modular polyketide synthase

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Taxol biosynthesis: Taxane 13α-hydroxylase is a cytochrome P450-dependent monooxygenase

Jennewein, S., Rithner, C. D., Williams, R. M., & Croteau, R. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251539398 · Cited by 241

Cyclodipeptide synthases are a family of tRNA-dependent peptide bond–forming enzymes

Gondry, M., Sauguet, L., Belin, P., Thai, R., Amouroux, R., Tellier, C., Tuphile, K., Jacquet, M., Braud, S., Courçon, M., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.175 · Cited by 239

Lyngbyatoxin Biosynthesis: Sequence of Biosynthetic Gene Cluster and Identification of a Novel Aromatic Prenyltransferase

Edwards, D. J., & Gerwick, W. H. (2004) · Journal of the American Chemical Society · doi:10.1021/ja047876g · Cited by 236

Lovastatin Nonaketide Synthase Catalyzes an Intramolecular Diels−Alder Reaction of a Substrate Analogue

Auclair, K., Sutherland, A., Kennedy, J., Witter, D. J., Van den Heever, J. P., Hutchinson, C. R., & Vederas, J. C. (2000) · Journal of the American Chemical Society · doi:10.1021/ja003216+ · Cited by 235

Reconstitution and Characterization of the Escherichia coli Enterobactin Synthetase from EntB, EntE, and EntF

Gehring, A. M., Mori, I., & Walsh, C. T. (1998) · Biochemistry · doi:10.1021/bi9726584 · Cited by 235

Three monophyletic superfamilies account for the majority of the known glycosyltransferases

Liu, J., & Mushegian, A. (2003) · Protein Science · doi:10.1110/ps.0302103 · Cited by 234

Genome Mining for Novel Natural Product Discovery

Challis, G. L. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm700948z · Cited by 231

Strictosidine Synthase: Mechanism of a Pictet−Spengler Catalyzing Enzyme

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Identification of a Baeyer–Villiger monooxygenase sequence motif

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Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli

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Thiostrepton Biosynthesis: Prototype for a New Family of Bacteriocins

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Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis

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Analysis of the prodiginine biosynthesis gene cluster of Streptomyces coelicolor A3(2): new mechanisms for chain initiation and termination in modular multienzymes

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Polyisoprenoids: Structure, biosynthesis and function

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Cytochrome P450 Taxadiene 5α-Hydroxylase, a Mechanistically Unusual Monooxygenase Catalyzing the First Oxygenation Step of Taxol Biosynthesis

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Molecular cloning of a cytochrome P450 taxane 10β-hydroxylase cDNA from Taxus and functional expression in yeast

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Chimeras of Two Isoprenoid Synthases Catalyze All Four Coupling Reactions in Isoprenoid Biosynthesis

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Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin

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Total biosynthesis: in vitro reconstitution of polyketide and nonribosomal peptide pathways

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Structural insights into nonribosomal peptide enzymatic assembly lines

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Biosynthesis and Structures of Cyclomarins and Cyclomarazines, Prenylated Cyclic Peptides of Marine Actinobacterial Origin

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Biosynthesis of the Sesquiterpene Antibiotic Albaflavenone in Streptomyces coelicolor A3(2)

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Thiopeptide Biosynthesis Featuring Ribosomally Synthesized Precursor Peptides and Conserved Posttranslational Modifications

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Biosynthesis of L-p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics

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Metamorphic enzyme assembly in polyketide diversification

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Biosynthesis of the salinosporamide A polyketide synthase substrate chloroethylmalonyl-coenzyme A from S -adenosyl- l -methionine

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Convergence of isoprene and polyketide biosynthetic machinery: Isoprenyl- S -carrier proteins in the pksX pathway of Bacillus subtilis

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Altering the glycosylation pattern of bioactive compounds

Méndez, C., & Salas, J. A. (2001) · Trends in Biotechnology · doi:10.1016/s0167-7799(01)01765-6 · Cited by 175

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The biosynthetic gene cluster for the macrolactone ring of the immunosuppressant FK506

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In vitro characterization of IroB, a pathogen-associated C -glycosyltransferase

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Nosiheptide Biosynthesis Featuring a Unique Indole Side Ring Formation on the Characteristic Thiopeptide Framework

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Ribosomally Synthesized Thiopeptide Antibiotics Targeting Elongation Factor Tu

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Equisetin biosynthesis in Fusarium heterosporum

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Working outside the protein‐synthesis rules: insights into non‐ribosomal peptide synthesis

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Thaxtomin biosynthesis: the path to plant pathogenicity in the genus Streptomyces

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Crystal Structure of OxyB, a Cytochrome P450 Implicated in an Oxidative Phenol Coupling Reaction during Vancomycin Biosynthesis

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Tandem Action of Glycosyltransferases in the Maturation of Vancomycin and Teicoplanin Aglycones: Novel Glycopeptides,

Losey, H. C., Peczuh, M. W., Chen, Z., Eggert, U. S., Dong, S. D., Pelczer, I., Kahne, D., & Walsh, C. T. (2001) · Biochemistry · doi:10.1021/bi010050w · Cited by 159

Enzymatic tools for engineering natural product glycosylation

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‘Sweetening’ natural products via glycorandomization

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Ribosomal Synthesis of Tricyclic Depsipeptides in Bloom‐Forming Cyanobacteria

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Selective interaction between nonribosomal peptide synthetases is facilitated by short communication-mediating domains

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Genome Mining in Streptomyces coelicolor: Molecular Cloning and Characterization of a New Sesquiterpene Synthase

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Formation of Unusual Sugars: Mechanistic Studies and Biosynthetic Applications

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Evidence that Biosynthesis of the Neurotoxic Alkaloids Anatoxin-a and Homoanatoxin-a in the Cyanobacterium Oscillatoria PCC 6506 Occurs on a Modular Polyketide Synthase Initiated by l -Proline

Méjean, A., Mann, S., Maldiney, T., Vassiliadis, G., Lequin, O., & Ploux, O. (2009) · Journal of the American Chemical Society · doi:10.1021/ja9024353 · Cited by 154

GliP, a Multimodular Nonribosomal Peptide Synthetase inAspergillus fumigatus, Makes the Diketopiperazine Scaffold of Gliotoxin

Balibar, C. J., & Walsh, C. T. (2006) · Biochemistry · doi:10.1021/bi061845b · Cited by 152

Cyclopiazonic Acid Biosynthesis in Aspergillus sp.: Characterization of a Reductase-like R* Domain in Cyclopiazonate Synthetase That Forms and Releases cyclo-Acetoacetyl- l -tryptophan

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Biosynthesis of Pipecolic Acid by RapL, a Lysine Cyclodeaminase Encoded in the Rapamycin Gene Cluster

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Elucidation of the Kijanimicin Gene Cluster: Insights into the Biosynthesis of Spirotetronate Antibiotics and Nitrosugars

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Terrequinone A biosynthesis through L-tryptophan oxidation, dimerization and bisprenylation

Balibar, C. J., Howard‐Jones, A. R., & Walsh, C. T. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.20 · Cited by 147

Discovering the Hidden Secondary Metabolome of Myxococcus xanthus : a Study of Intraspecific Diversity

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Characterization of the Cereulide NRPS α-Hydroxy Acid Specifying Modules: Activation of α-Keto Acids and Chiral Reduction on the Assembly Line

Magarvey, N. A., Ehling‐Schulz, M., & Walsh, C. T. (2006) · Journal of the American Chemical Society · doi:10.1021/ja0640187 · Cited by 143

2-Deoxystreptamine: Central Scaffold of Aminoglycoside Antibiotics

Busscher, G. F., Rutjes, F. P. J. T., & van Delft, F. L. (2005) · Chemical Reviews · doi:10.1021/cr0404085 · Cited by 142

Opportunities in metabolic engineering to facilitate scalable alkaloid production

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Biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds

Flatt, P. M., & Mahmud, T. (2007) · Natural Product Reports · doi:10.1039/b603816f · Cited by 138

Investigating the Initial Steps in the Biosynthesis of Cyanobacterial Sunscreen Scytonemin

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Total Synthesis of Thiostrepton. Retrosynthetic Analysis and Construction of Key Building Blocks

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Biosynthesis of the orthosomycin antibiotic avilamycin A: deductions from the molecular analysis of the avi biosynthetic gene cluster of Streptomyces viridochromogenes Tü57 and production of new antibiotics

Weitnauer, G., Mühlenweg, A., Trefzer, A. C., Hoffmeister, D., Süßmuth, R. D., Jung, G., Welzel, K., Vente, A., Girreser, U., & Bechthold, A. (2001) · Chemistry & Biology · doi:10.1016/s1074-5521(01)00040-0 · Cited by 132

Formation of novel secondary metabolites by bacterial multimodular assembly lines: deviations from textbook biosynthetic logic

Wenzel, S. C., & Müller, R. (2005) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2005.08.001 · Cited by 132

A Complete Gene Cluster from Streptomyces nanchangensis NS3226 Encoding Biosynthesis of the Polyether Ionophore Nanchangmycin

Sun, Y., Zhou, X., Dong, H. F., Guo-quan, T., Wang, M., Wang, B., & Deng, Z. (2003) · Chemistry & Biology · doi:10.1016/s1074-5521(03)00092-9 · Cited by 127

Advancing chemistry and biology through diversity-oriented synthesis of natural product-like libraries

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Reconstitution and Characterization of the Vibrio cholerae Vibriobactin Synthetase from VibB, VibE, VibF, and VibH

Keating, T. A., Marshall, C. G., & Walsh, C. T. (2000) · Biochemistry · doi:10.1021/bi0016523 · Cited by 126

Characterization of Kinetics and Products of the Baeyer−Villiger Oxygenase MtmOIV, The Key Enzyme of the Biosynthetic Pathway toward the Natural Product Anticancer Drug Mithramycin from Streptomyces a rgillaceus

Gibson, M., Nur‐e‐Alam, M., Lipata, F. M., Oliveira, M., & Rohr, J. (2005) · Journal of the American Chemical Society · doi:10.1021/ja055750t · Cited by 125

Ribosomal Synthesis of Tricyclic Depsipeptides in Bloom‐Forming Cyanobacteria

Ziemert, N., Ishida, K., Liaimer, A., Hertweck, C., & Dittmann, E. (2008) · Angewandte Chemie · doi:10.1002/ange.200802730 · Cited by 125

Insights into Polyether Biosynthesis from Analysis of the Nigericin Biosynthetic Gene Cluster in Streptomyces sp. DSM4137

Harvey, B. M., Mironenko, T., Sun, Y., Hong, H., Deng, Z., Leadlay, P. F., Weissman, K. J., & Haydock, S. F. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.05.011 · Cited by 124

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Kadi, N., Oves‐Costales, D., Barona‐Gómez, F., & Challis, G. L. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.23 · Cited by 123

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Salas, A. P., Zhu, L., Sánchez, C., Braña, A. F., Rohr, J., Méndez, C., & Salas, J. A. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04777.x · Cited by 122

Post‐translational Modification in Microviridin Biosynthesis

Philmus, B. J., Christiansen, G., Yoshida, W. Y., & Hemscheidt, T. K. (2008) · ChemBioChem · doi:10.1002/cbic.200800560 · Cited by 122

Chemical biology of tetracycline antibioticsThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Systems and Chemical Biology, and has undergone the Journal's usual peer review process.

Zakeri, B., & Wright, G. D. (2008) · Biochemistry and Cell Biology · doi:10.1139/o08-002 · Cited by 120

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Chau, M., Jennewein, S., Walker, K. D., & Croteau, R. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.02.025 · Cited by 117

Molecular cloning and characterization of a cytochrome P450 taxoid 2$alpha;-hydroxylase involved in Taxol biosynthesis*1, *2

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Characterization of the Surfactin Synthetase C-Terminal Thioesterase Domain as a Cyclic Depsipeptide Synthase

Tseng, C. C., Bruner, S. D., Kohli, R. M., Marahiel, M. A., Walsh, C. T., & Sieber, S. A. (2002) · Biochemistry · doi:10.1021/bi026592a · Cited by 116

Mechanism of Taxadiene Synthase, a Diterpene Cyclase That Catalyzes the First Step of Taxol Biosynthesis in Pacific Yew

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Characterization of the Saframycin A Gene Cluster fromStreptomyces lavendulaeNRRL 11002 Revealing a Nonribosomal Peptide Synthetase System for Assembling the Unusual Tetrapeptidyl Skeleton in an Iterative Manner

Li, L., Deng, W., Song, J., Ding, W., Zhao, Q., Peng, C., Song, W.-W., Tang, G., & Liu, W. (2007) · Journal of Bacteriology · doi:10.1128/jb.00826-07 · Cited by 114

Intramolecular cyclizations of polyketide biosynthesis: mining for a “Diels–Alderase”?

Kelly, W. L. (2008) · Organic & Biomolecular Chemistry · doi:10.1039/b814552k · Cited by 113

Oxidase Domains in Epothilone and Bleomycin Biosynthesis: Thiazoline to Thiazole Oxidation during Chain Elongation

Schneider, T. L., Shen, B., & Walsh, C. T. (2003) · Biochemistry · doi:10.1021/bi034792w · Cited by 108

Glycopeptide antibiotic biosynthesis: Enzymatic assembly of the dedicated amino acid monomer ( S )-3,5-dihydroxyphenylglycine

Chen, H., Tseng, C. C., Hubbard, B. K., & Walsh, C. T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.221582098 · Cited by 105

Microbes Made to Order

Ferber, D. (2004) · Science · doi:10.1126/science.303.5655.158 · Cited by 101

The Hedamycin Locus Implicates a Novel Aromatic PKS Priming Mechanism

Bililign, T., Hyun, C., Williams, J. S., Czisny, A. M., & Thorson, J. S. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.04.016 · Cited by 101

Multienzyme docking in hybrid megasynthetases

Richter, C. D., Nietlispach, D., Broadhurst, R. W., & Weissman, K. J. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.61 · Cited by 100

Microbial genomes: dealing with diversity

Boucher, Y., Nesbø, C. L., & Doolittle, W. F. (2001) · Current Opinion in Microbiology · doi:10.1016/s1369-5274(00)00204-6 · Cited by 98

Pyocyanin Isolated from a Marine Microbial Population: Synergistic Production between Two Distinct Bacterial Species and Mode of Action

Angell, S., Bench, B. J., Williams, H. J., & Watanabe, C. M. H. (2006) · Chemistry & Biology · doi:10.1016/j.chembiol.2006.10.012 · Cited by 97

Structure and Action of the C–C Bond-forming Glycosyltransferase UrdGT2 Involved in the Biosynthesis of the Antibiotic Urdamycin

Mittler, M., Bechthold, A., & Schulz, G. E. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.06.005 · Cited by 96

Biosynthesis of Aminocyclitol‐Aminoglycoside Antibiotics and Related Compounds

Flatt, P. M., & Mahmud, T. (2007) · ChemInform · doi:10.1002/chin.200730265 · Cited by 95

Carrier Protein Structure and Recognition in Polyketide and Nonribosomal Peptide Biosynthesis

Lai, J. R., Koglin, A., & Walsh, C. T. (2006) · Biochemistry · doi:10.1021/bi061979p · Cited by 94

Enzymatic Generation of the Antimetabolite γ,γ-Dichloroaminobutyrate by NRPS and Mononuclear Iron Halogenase Action in a Streptomycete

Ueki, M., Galonić, D. P., Vaillancourt, F. H., Garneau‐Tsodikova, S., Yeh, E., Vosburg, D. A., Schroeder, F. C., Osada, H., & Walsh, C. T. (2006) · Chemistry & Biology · doi:10.1016/j.chembiol.2006.09.012 · Cited by 93

Enzymatic Generation of the Chromopyrrolic Acid Scaffold of Rebeccamycin by the Tandem Action of RebO and RebD

Howard‐Jones, A. R., & Walsh, C. T. (2005) · Biochemistry · doi:10.1021/bi051706e · Cited by 93

Crystal Structure of OxyC, a Cytochrome P450 Implicated in an Oxidative C–C Coupling Reaction during Vancomycin Biosynthesis

Pylypenko, O., Vitali, F., Zerbe, K., Robinson, J. A., & Schlichting, I. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306486200 · Cited by 93

Epothilone biosynthesis: assembly of the methylthiazolylcarboxy starter unit on the EpoB subunit

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An Enzymatic Cyclopentyl[b]indole Formation Involved in Scytonemin Biosynthesis

Balskus, E. P., & Walsh, C. T. (2009) · Journal of the American Chemical Society · doi:10.1021/ja906752u · Cited by 89

The biosynthesis of polyketide-derived polycyclic ethers

Gallimore, A. R. (2008) · Natural Product Reports · doi:10.1039/b807902c · Cited by 88

The Lyngbyatoxin Biosynthetic Assembly Line: Chain Release by Four-Electron Reduction of a Dipeptidyl Thioester to the Corresponding Alcohol

Read, J. A., & Walsh, C. T. (2007) · Journal of the American Chemical Society · doi:10.1021/ja077374d · Cited by 86

Biosynthesis of the Terpene Phenalinolactone in Streptomyces sp. Tü6071: Analysis of the Gene Cluster and Generation of Derivatives

Dürr, C., Schnell, H., Luzhetskyy, A. N., Murillo, R., Weber, M., Welzel, K., Vente, A., & Bechthold, A. (2006) · Chemistry & Biology · doi:10.1016/j.chembiol.2006.01.011 · Cited by 84

Comparative analysis and insights into the evolution of gene clusters for glycopeptide antibiotic biosynthesis

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The impact of transcriptome and proteome analyses on antibiotic drug discovery

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The C -Glycosyltransferase UrdGT2 Is Unselective toward d - and l -Configured Nucleotide-Bound Rhodinoses

Hoffmeister, D., Dräger, G., Ichinose, K., Rohr, J., & Bechthold, A. (2003) · Journal of the American Chemical Society · doi:10.1021/ja029645k · Cited by 83

Characterization of the Formation of the Pyrrole Moiety during Clorobiocin and Coumermycin A1 Biosynthesis

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