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Shen, Ben
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Shen, Ben

Faculty Member
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Positions

  • 2017 - co-Chair, Chemistry , Scripps Research
  • 2017 - Professor (Joint Appointment), Molecular Medicine , Scripps Research
  • 2011 - Professor, Chemistry , Scripps Research
  • 2011 - Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 2011 - Professor (Joint Appointment), The Worm Institute for Research and Medicine (WIRM) , Scripps Research
  • 2011 - 2017 Professor (Joint Appointment), Molecular Therapeutics , Scripps Research
  • 2005 - 2010 Principal Investigator, NCI UW National Cooperative Drug Discovery Group, University of Wisconsin-Madison
  • 2004 - 2010 School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison
  • 2004 - 2010 Charles M. Johnson Distinguished Chair, School of Pharmacy, University of Wisconsin-Madison
  • 2001 - 2003 Associate Professor, School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison
  • 1995 - 2001 Assistant Professor, Department of Chemistry, University of California, Davis
  • 1991 - 1995 Postdoctoral Research Associate, University of Wisconsin-Madison

Research Areas research areas

  • Drug Discovery (UMLS)

Contact

  • shenb@scripps.edu

Websites

  • Ben Shen, Ph.D.
  • Shen Laboratory
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Publications

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  • academic article

    • Zhang, X., King-Smith, E., Dong, L. B., Yang, L. C., Rudolf, J. D., Shen, B., Renata, H. Divergent synthesis of complex diterpenes through a hybrid oxidative approach Science  2020 369:799-806  DOI:10.1126/science.abb8271  PMID:32792393
    • Wang, Z., Liu, X., Peng, Y., Su, M., Zhu, S., Pan, J., Shen, B., Duan, Y., Huang, Y. Platensimycin-Encapsulated Liposomes or Micelles as Biosafe Nanoantibiotics Exhibited Strong Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus Infection in Mice Molecular Pharmaceutics  2020 17:2451-2462  DOI:10.1021/acs.molpharmaceut.0c00194  PMID:32519867
    • Zhou, W., Liang, H., Qin, X., Cao, D., Zhu, X., Ju, J., Shen, B., Duan, Y., Huang, Y. The isolation of pyrroloformamide congeners and characterization of their biosynthetic gene cluster Journal of Natural Products  2020 83:202-209  DOI:10.1021/acs.jnatprod.9b00321  PMID:32049520
    • Adhikari, A., Teijaro, C. N., Yan, X. H., Chang, C. Y., Gui, C., Liu, Y. C., Crnovcic, I., Yang, D., Annaval, T., Rader, C., Shen, B. Characterization of TnmH as an O-Methyltransferase Revealing Insights into Tiancimycin Biosynthesis and Enabling a Biocatalytic Strategy To Prepare Antibody-Tiancimycin Conjugates Journal of Medicinal Chemistry  2020 63:8432-8441  DOI:10.1021/acs.jmedchem.0c00799  PMID:32658465  PMCID:PMC7461649
    • Kalkreuter, E., Pan, G. H., Cepeda, A. J., Shen, B. Targeting bacterial genomes for natural product discovery Trends in Pharmacological Sciences  2020 41:13-26  DOI:10.1016/j.tips.2019.11.002  PMID:31822352  PMCID:PMC6938545
    • Steele, A. D., Teijaro, C. N., Yang, D., Shen, B. Leveraging a large microbial strain collection for natural product discovery Journal of Biological Chemistry  2019 294:16567-16576  DOI:10.1074/jbc.REV119.006514  PMID:31570525  PMCID:PMC6851301
    • Liang, H., Jiang, L., Jiang, Q., Shi, J., Xiang, J., Yan, X., Zhu, X., Zhao, L., Shen, B., Duan, Y., Huang, Y. A 3-hydroxy-3-methylglutaryl-CoA synthase-based probe for the discovery of the acyltransferase-less type I polyketide synthases Environmental Microbiology  2019  DOI:10.1111/1462-2920.14787  PMID:31435987
    • Wang, Z., Wen, Z., Liu, L., Zhu, X., Shen, B., Yan, X., Duan, Y., Huang, Y. Yangpumicins F and G, enediyne congeners from Micromonospora yangpuensis DSM 45577 Journal of Natural Products  2019 82:2483-2488  DOI:10.1021/acs.jnatprod.9b00229  PMID:31490685
    • Dong, L. B., Liu, Y. C., Cepeda, A. J., Kalkreuter, E., Deng, M. R., Rudolf, J. D., Chang, C., Joachimiak, A., Phillips, G. N., Shen, B. Characterization and crystal structure of a nonheme diiron monooxygenase involved in platensimycin and platencin biosynthesis Journal of the American Chemical Society  2019 141:12406-12412  DOI:10.1021/jacs.9b06183  PMID:31291107
    • Deng, Y., Weng, X., Li, Y., Su, M., Wen, Z., Ji, X., Ren, N., Shen, B., Duan, Y., Huang, Y. Late-stage functionalization of platensimycin leading to multiple analogues with improved antibacterial activity in vitro and in vivo Journal of Medicinal Chemistry  2019 62:6682-6693  DOI:10.1021/acs.jmedchem.9b00616  PMID:31265289
    • Su, M., Qiu, L., Deng, Y., Ruiz, C. H., Rudolf, J. D., Dong, L. B., Feng, X., Cameron, M. D., Shen, B., Duan, Y., Huang, Y. Evaluation of platensimycin and platensimycin-inspired thioether analogues against methicillin-resistant staphylococcus aureus in topical and systemic infection mouse models Molecular Pharmaceutics  2019 16:3065-3071  DOI:10.1021/acs.molpharmaceut.9b00293  PMID:31244223
    • Xu, Z., Fang, S. M., Bakowski, M. A., Rateb, M. E., Yang, D., Zhu, X., Huang, Y., Zhao, L. X., Jiang, Y., Duan, Y., Hull, M. V., McNamara, C. W., et al. Discovery of kirromycins with anti-Wolbachia activity from Streptomyces sp. CB00686 ACS Chemical Biology  2019 14:1174-1182  DOI:10.1021/acschembio.9b00086  PMID:31074963
    • Qiu, L., Wen, Z., Li, Y., Tian, K., Deng, Y., Shen, B., Duan, Y., Huang, Y. Stereoselective functionalization of platensimycin and platencin by sulfa-Michael/aldol reactions Organic & Biomolecular Chemistry  2019 17:4261-4272  DOI:10.1039/c9ob00324j  PMID:30816397
    • Dong, L. B., Zhang, X., Rudolf, J. D., Deng, M. R., Kalkreuter, E., Cepeda, A. J., Renata, H., Shen, B. Cryptic and stereospecific hydroxylation, oxidation, and reduction in platensimycin and platencin biosynthesis Journal of the American Chemical Society  2019 141:4043-4050  DOI:10.1021/jacs.8b13452  PMID:30735041
    • Teijaro, C. N., Adhikari, A., Shen, B. Challenges and opportunities for natural product discovery, production, and engineering in native producers versus heterologous hosts Journal of Industrial Microbiology & Biotechnology  2019 46:433-444  DOI:10.1007/s10295-018-2094-5  PMID:30426283  PMCID:PMC6405299
    • Den, Y., Su, M., Kang, D., Liu, X., Wen, Z., Li, Y., Qiu, L., Shen, B., Duan, Y., Huang, Y. Semisynthesis of platensimycin derivatives with antibiotic activities in mice via Suzuki-Miyaura cross-coupling reactions Journal of Medicinal Chemistry  2018 61:11341-11348  DOI:10.1021/acs.jmedchem.8b01580  PMID:30461269
    • Kearney, S. E., Zahoranszky-Kohalmi, G., Brimacombe, K. R., Henderson, M. J., Lynch, C., Zhao, T., Wan, K. K., Itkin, Z., Dillon, C., Shen, M., Cheff, D. M., Lee, T. D., et al. Canvass: a crowd-sourced, natural-product screening library for exploring biological space ACS Central Science  2018 4:1727-1741  DOI:10.1021/acscentsci.8b00747  PMID:30648156  PMCID:PMC6311695
    • Xu, Z., Pan, G., Zhou, H., Shen, B. Discovery and characterization of 1-aminocyclopropane-1-carboxylic acid synthase of bacterial origin Journal of the American Chemical Society  2018 140:16957-16961  DOI:10.1021/jacs.8b11463  PMID:30472830
    • Tian, K., Deng, Y., Qiu, L., Zhu, X., Shen, B., Duan, Y., Huang, Y. Semisynthesis and biological evaluation of platensimycin analogues with varying aminobenzoic acids ChemistrySelect  2018 3:12625-12629  DOI:10.1002/slct.201802475
    • Rudolf, J. D., Dong, L. B., Zhang, X., Renata, H., Shen, B. Cytochrome P450-catalyzed hydroxylation initiating ether formation in platensimycin biosynthesis Journal of the American Chemical Society  2018 140:12349-12353  DOI:10.1021/jacs.8b08012  PMID:30216060
    • Yan, X., Chen, J. J., Adhikari, A., Teijaro, C. N., Ge, H., Crnovcic, I., Chang, C. Y., Annaval, T., Yang, D., Rader, C., Shen, B. Comparative studies of the biosynthetic gene clusters for anthraquinone-fused enediynes shedding light into the tailoring steps of tiancimycin biosynthesis Organic Letters  2018 20:5918-5921  DOI:10.1021/acs.orglett.8b02584  PMID:30212211
    • Chang, C. Y., Yan, X., Crnovcic, I., Annaval, T., Chang, C., Nocek, B., Rudolf, J. D., Yang, D., Hindra, Babnigg, G., Joachimiak, A., Phillips, G. N., et al. Resistance to enediyne antitumor antibiotics by sequestration Cell Chemical Biology  2018 25:1075-1085  DOI:10.1016/j.chembiol.2018.05.012  PMID:29937405
    • Crnovcic, I., Gan, F., Yang, D., Dong, L. B., Schultz, P. G., Shen, B. Activities of recombinant human bleomycin hydrolase on bleomycins and engineered analogues revealing new opportunities to overcome bleomycin-induced pulmonary toxicity Bioorganic & Medicinal Chemistry Letters  2018 28:2670-2674  DOI:10.1016/j.bmcl.2018.04.065  PMID:29730026
    • Annaval, T., Han, L., Rudolf, J. D., Xie, G., Yang, D., Chang, C. Y., Ma, M., Crnovcic, I., Miller, M. D., Soman, J., Xu, W., Phillips Jr., G. N., et al. Biochemical and structural characterization of TtnD, a prenylated FMN-dependent decarboxylase from the tautomycetin biosynthetic pathway ACS Chemical Biology  2018 13:2728-2738  DOI:10.1021/acschembio.8b00673  PMID:30152678
    • Kwong, T., Ma, M., Pan, G., Hindra, Yang, D., Yang, C., Lohman, J. R., Rudolf, J. D., Cleveland, J. L., Shen, B. P450-catalyzed tailoring steps in leinamycin biosynthesis featuring regio- and stereoselective hydroxylations and substrate promiscuities Biochemistry  2018 57:5005-5013  DOI:10.1021/acs.biochem.8b00623  PMID:30070831  PMCID:PMC6211295
    • Dong, L. B., Rudolf, J. D., Deng, M. R., Yan, X., Shen, B. Discovery of the tiancilactone antibiotics by genome mining of atypical bacterial type II diterpene synthases ChemBioChem  2018 19:1727-1733  DOI:10.1002/cbic.201800285  PMID:29806086
    • Murray, V., Chen, J. K., Yang, D., Shen, B. The genome-wide sequence specificity of DNA cleavage by bleomycin analogues in human cells Bioorganic & Medicinal Chemistry  2018 26:4168-4178  DOI:10.1016/j.bmc.2018.07.006  PMID:30006142
    • Kong, J. Q., Yi, L., Xiong, Y., Huang, Y., Yang, D., Yan, X., Shen, B., Duan, Y., Zhu, X. The discovery and development of microbial bleomycin analogues Applied Microbiology and Biotechnology  2018 102:6791-6798  DOI:10.1007/s00253-018-9129-8  PMID:29876605
    • Wang, N., Rudolf, J. D., Dong, L. B., Osipiuk, J., Hatzos-Skintges, C., Endres, M., Chang, C. Y., Babnigg, G., Joachimiak, A., Phillips, G. N., Shen, B. Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme Nature Chemical Biology  2018 14:730-737  DOI:10.1038/s41589-018-0061-0  PMID:29867143  PMCID:PMC6008203
    • Jiang, L., Pu, H., Xiang, J., Su, M., Yan, X., Yang, D., Zhu, X., Shen, B., Duan, Y., Huang, Y. Huanglongmycin A-C, cytotoxic polyketides biosynthesized by a putative type II polyketide synthase from Streptomyces sp. CB09001 Frontiers in Chemistry  2018 6  DOI:10.3389/fchem.2018.00254  PMID:30013965  PMCID:PMC6036704
    • Dong, L. B., Rudolf, J. D., Kang, D., Wang, N., He, C. Q., Deng, Y., Huang, Y., Houk, K. N., Duan, Y., Shen, B. Biosynthesis of thiocarboxylic acid-containing natural products Nature Communications  2018 9  DOI:10.1038/s41467-018-04747-y  PMID:29915173  PMCID:PMC6006322
    • Chang, C. Y., Lohman, J. R., Huang, T., Michalska, K., Bigelow, L., Rudolf, J. D., Jedrzejczak, R., Yan, X., Ma, M., Babnigg, G., Joachimiak, A., Phillips, G. N., et al. Structural insights into the free-standing condensation enzyme SgcC5 catalyzing ester-bond formation in the biosynthesis of the enediyne antitumor antibiotic C-1027 Biochemistry  2018 57:3278-3288  DOI:10.1021/acs.biochem.8b00174  PMID:29533601
    • Deng, Y., Kang, D., Shi, J., Zhou, W., Sun, A. J., Ju, J., Zhu, X., Shen, B., Duan, Y., Huang, Y. The semi-synthesis, biological evaluation and docking analysis of the oxime, hydrazine and hydrazide derivatives of platensimycin MedChemComm  2018 9:789-794  DOI:10.1039/c8md00081f
    • Chen, J. J., Rateb, M. E., Love, M. S., Xu, Z., Yang, D., Zhu, X., Huang, Y., Zhao, L. X., Jiang, Y., Duan, Y., McNamara, C. W., Shen, B. Herbicidins from Streptomyces sp. CB01388 showing anti-cryptosporidium activity Journal of Natural Products  2018 81:791-797  DOI:10.1021/acs.jnatprod.7b00850  PMID:29469575
    • Yan, X., Hindra, Ge, H., Yang, D., Huang, T., Crnovcic, I., Chang, C. Y., Fang, S. M., Annaval, T., Zhu, X., Huang, Y., Zhao, L. X., et al. Discovery of alternative producers of the enediyne antitumor antibiotic C-1027 with high titers Journal of Natural Products  2018 81:594-599  DOI:10.1021/acs.jnatprod.7b01013  PMID:29345939
    • Liu, L., Pan, J., Wang, Z., Yan, X., Yang, D., Zhu, X., Shen, B., Duan, Y., Huang, Y. Ribosome engineering and fermentation optimization leads to overproduction of tiancimycin A, a new enediyne natural product from Streptomyces sp CB03234 Journal of Industrial Microbiology & Biotechnology  2018 45:141-151  DOI:10.1007/s10295-018-2014-8  PMID:29396746
    • Guo, X., Crnovcic, I., Chang, C. Y., Luo, J., Lohman, J. R., Papinski, M., Bechthold, A., Horsman, G. P., Shen, B. PokMT1 from the polyketomycin biosynthetic machinery of Streptomyces diastatochromogenes Tü6028 belongs to the emerging family of C-methyltransferases that act on CoA-activated aromatic substrates Biochemistry  2018 57:1003-1011  DOI:10.1021/acs.biochem.7b01219
    • Qu, L., Tian, K., Wen, Z., Deng, Y., Kang, D., Liang, H., Zhu, X., Shen, B., Duan, Y., Huang, Y. Biomimetic stereoselective sulfa-michael addition leads to platensimycin and platencin sulfur analogues against methicillin-resistant Staphylococcus aureus Journal of Natural Products  2018 81:316-322  DOI:10.1021/acs.jnatprod.7b00745  PMID:29389125
    • Zhu, X., Kong, J., Yang, H., Huang, R., Huang, Y., Yang, D., Shen, B., Duan, Y. Strain improvement by combined UV mutagenesis and ribosome engineering and subsequent fermentation optimization for enhanced 6 '-deoxy-bleomycin Z production Applied Microbiology and Biotechnology  2018 102:1651-1661  DOI:10.1007/s00253-017-8705-7  PMID:29279956
    • Nejad, M. I., Yang, D., Shen, B., Gates, K. S. Oxidative activation of leinamycin E1 triggers alkylation of guanine residues in double-stranded DNA Chemical Communications  2018 54:256-259  DOI:10.1039/c7cc08482j  PMID:29231931
    • Yang, D., Hindra, Dong, L. B., Crnovcic, I., Shen, B. Engineered production and evaluation of 6'-deoxy-tallysomycin H-1 revealing new insights into the structure-activity relationship of the anticancer drug bleomycin Journal of Antibiotics  2018 71:97-103  DOI:10.1038/ja.2017.93  PMID:28831149
    • Pan, G., Xu, Z., Guo, Z., Hindra, Ma, M., Yang, D., Zhou, H., Gansemans, Y., Zhu, X., Huang, Y., Zhao, L. X., Jiang, Y., et al. Discovery of the leinamycin family of natural products by mining actinobacterial genomes Proceedings of the National Academy of Sciences of the United States of America  2017 114:E11131-E11140  DOI:10.1073/pnas.1716245115  PMID:29229819  PMCID:PMC5748217
    • Yan, X., Chen, J. J., Adhikari, A., Yang, D., Crnovcic, I., Wang, N., Chang, C. Y., Rader, C., Shen, B. Genome mining of micromonospora yangpuensis DSM 45577 as a producer of an anthraquinone-fused enediyne Organic Letters  2017 19:6192-6195  DOI:10.1021/acs.orglett.7b03120  PMID:29086572
    • Rudolf, J. D., Chang, C. Y., Ma, M., Shen, B. Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function Natural Product Reports  2017 34:1141-1172  DOI:10.1039/c7np00034k  PMID:28758170  PMCID:PMC5585785
    • Falzone, M., Crespo, E., Jones, K., Khan, G., Korn, V. L., Patel, A., Patel, M., Patel, K., Perkins, C., Siddiqui, S., Stenger, D., Yu, E., et al. Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of L-aspartic acid Journal of Antibiotics  2017 70:828-831  DOI:10.1038/ja.2017.49  PMID:28465627
    • Zhang, B., Xu, Z., Teng, Q., Pan, G., Ma, M., Shen, B. A long-range acting dehydratase domain as the missing link for C17-dehydration in iso-migrastatin biosynthesis Angewandte Chemie-International Edition  2017 56:7247-7251  DOI:10.1002/anie.201703588  PMID:28464455
    • Rudolf, J. D., Dong, L. B., Shen, B. Platensimycin and platencin: Inspirations for chemistry, biology, enzymology, and medicine Biochemical Pharmacology  2017 133:139-151  DOI:10.1016/j.bcp.2016.11.013  PMID:27865713  PMCID:PMC5410400
    • Yang, D., Rateb, M. E., Wang, N., Shen, B. Competition and co-regulation of spirotoamide and tautomycetin biosynthesis in Streptomyces griseochromogenes, and isolation and structural elucidation of spirotoamide C and D Journal of Antibiotics  2017 70:710-714  DOI:10.1038/ja.2017.13  PMID:28196980
    • Chen, J. K., Yang, D., Shen, B., Murray, V. Bleomycin analogues preferentially cleave at the transcription start sites of actively transcribed genes in human cells International Journal of Biochemistry & Cell Biology  2017 85:56-65  DOI:10.1016/j.biocel.2017.02.001  PMID:28167289
    • Guo, Z., Pan, G., Xu, Z., Yang, D., Hindra, Zhu, X., Huang, Y., Zhao, L. X., Jiang, Y., Duan, Y., Shen, B. New isofuranonaphthoquinones and isoindolequinones from Streptomyces sp. CB01883 Journal of Antibiotics  2017 70:414-422  DOI:10.1038/ja.2016.122  PMID:27731333
    • Hindra, Yang, D., Teng, Q., Dong, L. B., Crnovcic, I., Huang, T., Ge, H., Shen, B. Genome mining of streptomyces mobaraensis DSM40847 as a bleomycin producer providing a biotechnology platform to engineer designer bleomycin analogues Organic Letters  2017 19:1386-1389  DOI:10.1021/acs.orglett.7b00283  PMID:28256838
    • Dong, L. B., Rudolf, J. D., Lin, L., Ruiz, C., Cameron, M. D., Shen, B. In vivo instability of platensimycin and platencin: Synthesis and biological evaluation of urea- and carbamate-platensimycin Bioorganic & Medicinal Chemistry  2017 25:1990-1996  DOI:10.1016/j.bmc.2017.02.028  PMID:28237556
    • Qiu, L., Tian, K., Pan, J., Jiang, L., Yang, H., Zhu, X., Shen, B., Duan, Y., Huang, Y. A facile semi-synthetic approach towards halogen-substituted aminobenzoic acid analogues of platensimycin Tetrahedron  2017 73:771-775  DOI:10.1016/j.tet.2016.12.059
    • Ma, M., Rateb, M. E., Yang, D., Rudolf, J. D., Zhu, X., Huang, Y., Zhao, L. X., Jiang, Y., Duan, Y., Shen, B. Germicidins H-J from streptomyces sp CB00361 Journal of Antibiotics  2017 70:200-203  DOI:10.1038/ja.2016.100
    • Rudolf, J. D., Dong, L. B., Manoogian, K., Shen, B. Biosynthetic origin of the ether ring in platensimycin Journal of the American Chemical Society  2016 138:16711-16721  DOI:10.1021/jacs.6b09818  PMID:27966343
    • Dong, L. B., Rudolf, J. D., Shen, B. Antibacterial sulfur-containing platensimycin and platencin congeners from Streptomyces platensis SB12029 Bioorganic & Medicinal Chemistry  2016 24:6348-6353  DOI:10.1016/j.bmc.2016.04.026  PMID:27134119  PMCID:PMC5063666
    • Huang, Y., Yang, D., Pan, G., Tang, G. L., Shen, B. Characterization of LnmO as a pathway-specific Crp/Fnr-type positive regulator for leinamycin biosynthesis in Streptomyces atroolivaceus and its application for titer improvement Applied Microbiology and Biotechnology  2016 100:10555-10562  DOI:10.1007/s00253-016-7864-2  PMID:27704182  PMCID:PMC5121087
    • Chen, J. K., Yang, D., Shen, B., Neilan, B. A., Murray, V. Zorbamycin has a different DNA sequence selectivity compared with bleomycin and analogues Bioorganic & Medicinal Chemistry  2016 24:6094-6101  DOI:10.1016/j.bmc.2016.09.072  PMID:27745992
    • Yan, X., Ge, H., Huang, T., Hindra, Yang, D., Teng, Q., Crnovcic, I., Li, X., Rudolf, J. D., Lohman, J. R., Gansemans, Y., Zhu, X., et al. Strain prioritization and genome mining for enediyne natural products MBio  2016 7  DOI:10.1128/mBio.02104-16  PMID:27999165  PMCID:PMC5181780
    • Huang, T., Chang, C. Y., Lohman, J. R., Rudolf, J. D., Kim, Y., Chang, C., Yang, D., Ma, M., Yan, X., Crnovcic, I., Bigelow, L., Clancy, S., et al. Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027 Journal of Antibiotics  2016 69:731-740  DOI:10.1038/ja.2016.88  PMID:27406907  PMCID:PMC5083130
    • Dong, L. B., Rudolf, J. D., Shen, B. A mutasynthetic library of platensimycin and platencin analogues Organic Letters  2016 18:4606-4609  DOI:10.1021/acs.orglett.6602248  PMID:27599271  PMCID:PMC5048679
    • Chang, C. Y., Lohman, J. R., Cao, H., Tan, K., Rudolf, J. D., Ma, M., Xu, W., Bingman, C. A., Yennamalli, R. M., Bigelow, L., Babnigg, G., Yan, X., et al. Crystal structures of SgcE6 and SgcC, the two-component monooxygenase that catalyzes hydroxylation of a carrier protein-tethered substrate during the biosynthesis of the enediyne antitumor antibiotic C-1027 in streptomyces globisporus Biochemistry  2016 55:5142-5154  DOI:10.1021/acs.biochem.6b00713  PMID:27560143  PMCID:PMC5024704
    • Li, W., Li, X., Huang, T., Teng, Q., Crnovcic, I., Rader, C., Shen, B. Engineered production of cancer targeting peptide (CTP)-containing C-1027 in Streptomyces globisporus and biological evaluation Bioorganic & Medicinal Chemistry  2016 24:3887-3892  DOI:10.1016/j.bmc.2016.04.017  PMID:27094150  PMCID:PMC4972678
    • Rudolf, J. D., Dong, L. B., Cao, H., Hatzos-Skintges, C., Osipiuk, J., Endres, M., Chang, C. Y., Ma, M., Babnigg, G., Joachimiak, A., Phillips, G. N., Shen, B. Structure of the ent-copalyl diphosphate synthase PtmT2 from streptomyces platensis CB00739, a bacterial type II diterpene synthase Journal of the American Chemical Society  2016 138:10905-10915  DOI:10.1021/jacs.6b04317  PMID:27490479  PMCID:PMC5013971
    • Shi, J., Pan, J., Liu, L., Yang, D., Lu, S., Zhu, X., Shen, B., Duan, Y., Huang, Y. Titer improvement and pilot-scale production of platensimycin from Streptomyces platensis SB12026 Journal of Industrial Microbiology & Biotechnology  2016 43:1027-1035  DOI:10.1007/s10295-016-1769-z  PMID:27126098  PMCID:PMC5056013
    • Rudolf, J. D., Yan, X., Shen, B. Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery Journal of Industrial Microbiology & Biotechnology  2016 43:261-276  DOI:10.1007/s10295-015-1671-0  PMID:26318027  PMCID:PMC4753101
    • Zhang, B., Yang, D., Yan, Y., Pan, G., Xiang, W., Shen, B. Overproduction of lactimidomycin by cross-overexpression of genes encoding Streptomyces antibiotic regulatory proteins Applied Microbiology and Biotechnology  2016 100:2267-2277  DOI:10.1007/s00253-015-7119-7  PMID:26552797  PMCID:PMC4758858
    • Smanski, M. J., Zhou, H., Claesen, J., Shen, B., Fischbach, M. A., Voigt, C. A. Synthetic biology to access and expand nature's chemical diversity Nature Reviews Microbiology  2016 14:135-149  DOI:10.1038/nrmicro.2015.24  PMID:26876034  PMCID:PMC5048682
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    • Ju, J. H., Ozanick, S. G., Shen, B., Thomas, M. G. Conversion of (2s)-arginine to (2s,3r)-capreomycidine by vioc and viod from the viomycin biosynthetic pathway of streptomyces sp strain atcc11861 ChemBioChem  2004 5:1281-1285  DOI:10.1002/cbic.200400136  PMID:15368582
    • Murrell, J. M., Liu, W., Shen, B. Biochemical characterization of the sgca1 alpha-d-glucopyranosyl-1-phosphate thymidylyltransferase from the enediyne antitumor antibiotic c-1027 biosynthetic pathway and overexpression of sgca1 in streptomyces globisporus to improve c-1027 production Journal of Natural Products  2004 67:206-213  DOI:10.1021/np0340403  PMID:14987060
    • Chapados, B. R., Hosfield, D. J., Han, S., Qiu, J. Z., Yelent, B., Shen, B. H., Tainer, J. A. Structural basis for FEN-1 substrate specificity and PCNA-mediated activation in DNA replication and repair Cell  2004 116:39-50  DOI:10.1016/s0092-8674(03)01036-5  PMID:14718165
    • Shen, B. Accessing natural products by combinatorial biosynthesis Science's STKE : Signal Transduction Knowledge Environment  2004 2004:pe14  DOI:10.1126/stke.2252004pe14  PMID:15039491
    • Tang, G. L., Cheng, Y. Q., Shen, B. Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase Chemistry & Biology  2004 11:33-45  DOI:10.1016/j.chembiol.2003.12.014  PMID:15112993
    • Christenson, S. D., Wu, W. M., Spies, M. A., Shen, B., Toney, M. D. Kinetic analysis of the 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic c-1027 biosynthesis Biochemistry  2003 42:12708-12718  DOI:10.1021/bi035223r  PMID:14580219
    • Shen, B., Liu, W., Nonaka, K. Enediyne natural products: Biosynthesis and prospect towards engineering novel antitumor agents Current Medicinal Chemistry  2003 10:2317-2325  DOI:10.2174/0929867033456701  PMID:14529344
    • Liu, W., Ahlert, J., Gao, Q. J., Wendt-Pienkowski, E., Shen, B., Thorson, J. S. Rapid pcr amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model Proceedings of the National Academy of Sciences of the United States of America  2003 100:11959-11963  DOI:10.1073/pnas.2034291100  PMID:14528002  PMCID:PMC218695
    • Du, L. C., Chen, M., Zhang, Y., Shen, B. Blmiii and bimiv nonribosornal peptide synthetase-catalyzed biosynthesis of the bleomycin bithiazole moiety involving both in cis and in trans aminoacylation Biochemistry  2003 42:9731-9740  DOI:10.1021/bi034817r  PMID:12911315
    • Schneider, T. L., Shen, B., Walsh, C. T. Oxidase domains in epothilone and bleomycin biosynthesis: Thiazoline to thiazole oxidation during chain elongation Biochemistry  2003 42:9722-9730  DOI:10.1021/bi034792w  PMID:12911314
    • Christenson, S. D., Liu, W., Toney, M. D., Shen, B. A novel 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic c-1027 biosynthesis Journal of the American Chemical Society  2003 125:6062-6063  DOI:10.1021/ja034609m  PMID:12785829
    • Shen, B. Polyketide biosynthesis beyond the type i, ii and iii polyketide synthase paradigms Current Opinion in Chemical Biology  2003 7:285-295  DOI:10.1016/s1367-5931(03)00020-6  PMID:12714063
    • Cheng, Y. Q., Tang, G. L., Shen, B. Type i polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis Proceedings of the National Academy of Sciences of the United States of America  2003 100:3149-3154  DOI:10.1073/pnas.0537286100  PMID:12598647  PMCID:PMC152261
    • Zazopoulos, E., Huang, K. X., Staffa, A., Liu, W., Bachmann, B. O., Nonaka, K., Ahlert, J., Thorson, J. S., Shen, B., Farnet, C. M. A genomics-guided approach for discovering and expressing cryptic metabolic pathways Nature Biotechnology  2003 21:187-190  DOI:10.1038/nbt784  PMID:12536216
    • Cheng, Y. Q., Tang, G. L., Shen, B. Identification and localization of the gene cluster encoding biosynthesis of the antitumor macrolactam leinamycin in streptomyces atroolivaceus s-140 Journal of Bacteriology  2002 184:7013-7024  DOI:10.1128/jb.184.24.7013-7024.2002  PMID:12446651
    • Kwon, H. J., Smith, W. C., Scharon, A. J., Hwang, S. H., Kurth, M. J., Shen, B. C-o bond formation by polyketide synthases Science  2002 297:1327-1330  DOI:10.1126/science.1073175  PMID:12193782
    • Liu, W., Christenson, S. D., Standage, S., Shen, B. Biosynthesis of the enediyne antitumor antibiotic c-1027 Science  2002 297:1170-1173  DOI:10.1126/science.1072110  PMID:12183628
    • Shen, B., Du, L. C., Sanchez, C., Edwards, D. J., Chen, M., Murrell, J. M. Cloning and characterization of the bleomycin biosynthetic gene cluster from streptomyces verticillus atcc15003 Journal of Natural Products  2002 65:422-431  DOI:10.1021/np010550q  PMID:11908996
    • Shen, B., Kwon, H. J. Macrotetrolide biosynthesis: A novel type ii polyketide synthase Chemical Record  2002 2:389-396  DOI:10.1002/tcr.10042  PMID:12469350
    • Shen, B., Du, L., Sanchez, C., Edwards, D. J., Chen, M., Murrell, J. M. The biosynthetic gene cluster for the anticancer drug bleomycin from streptomyces verticillus atcc15003 as a model for hybrid peptide-polyketide natural product biosynthesis Journal of Industrial Microbiology & Biotechnology  2001 27:378-385  DOI:10.1038/sj.jim.7000194  PMID:11774003
    • Chai, Q., Qiu, J., Chapados, B. R., Shen, B. Archaeoglobus fulgidus RNase HII in DNA replication: enzymological functions and activity regulation via metal cofactors Biochemical and Biophysical Research Communications  2001 286:1073-1081  DOI:10.1006/bbrc.2001.5523  PMID:11527410
    • Sanchez, C., Du, L. C., Edwards, D. J., Toney, M. D., Shen, B. Cloning and characterization of a phosphopantetheinyl transferase from streptomyces verticillus atcc15003, the producer of the hybrid peptide-polyketide antitumor drug bleomycin Chemistry & Biology  2001 8:725-738  DOI:10.1016/s1074-5521(01)00047-3  PMID:11451672
    • Kwon, H. J., Smith, W. C., Xiang, L. K., Shen, B. Cloning and heterologous expression of the macrotetrolide biosynthetic gene cluster revealed a novel polyketide synthase that lacks an acyl carrier protein Journal of the American Chemical Society  2001 123:3385-3386  DOI:10.1021/ja0100827  PMID:11457082
    • Rafanan, E. R., Le, L., Zhao, L. L., Decker, H., Shen, B. Cloning, sequencing, and heterologous expression of the elmghij genes involved in the biosynthesis of the polyketide antibiotic elloramycin from streptomyces olivaceus tu2353 Journal of Natural Products  2001 64:444-449  PMID:11325225
    • Du, L., Shen, B. Biosynthesis of hybrid peptide-polyketide natural products Current Opinion in Drug Discovery & Development  2001 4:215-228  PMID:11378961
    • Du, L. H., Sanchez, C., Shen, B. Hybrid peptide-polyketide natural products: Biosynthesis and prospects toward engineering novel molecules Metabolic Engineering  2001 3:78-95  DOI:10.1006/mben.2000.0171  PMID:11162234
    • Beynon, J., Rafanan, E. R., Jr., Shen, B., Fisher, A. J. Crystallization and preliminary x-ray analysis of tetracenomycin a2 oxygenase: A flavoprotein hydroxylase involved in polyketide biosynthesis Acta Crystallographica Section D-Biological Crystallography  2000 56:1647-1651  DOI:10.1107/s0907444900012695  PMID:11092935
    • Rafanan, E. R., Hutchinson, C. R., Shen, B. Triple hydroxylation of tetracenomycin a2 to tetracenomycin c involving two molecules of o-2 and one molecule of h2o Organic Letters  2000 2:3225-3227  PMID:11009387
    • Du, L. C., Chen, M., Sanchez, C., Shen, B. An oxidation domain in the blmiii non-ribosomal peptide synthetase probably catalyzing thiazole formation in the biosynthesis of the anti-tumor drug bleomycin in streptomyces verticillus atcc15003 FEMS Microbiology Letters  2000 189:171-175  DOI:10.1111/j.1574-6968.2000.tb09225.x  PMID:10930733
    • Du, L. C., Sanchez, C., Chen, M., Edwards, D. J., Shen, B. The biosynthetic gene cluster for the antitumor drug bleomycin from streptomyces verticillus atcc15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase Chemistry & Biology  2000 7:623-642  DOI:10.1016/s1074-5521(00)00011-9  PMID:11048953
    • Smith, W. C., Xiang, L. K., Shen, B. Genetic localization and molecular characterization of the nons gene required for macrotetrolide biosynthesis in streptomyces griseus dsm40695 Antimicrobial Agents and Chemotherapy  2000 44:1809-1817  DOI:10.1128/aac.44.7.1809-1817.2000  PMID:10858335
    • Liu, W., Shen, B. Genes for production of the enediyne antitumor antibiotic c-1027 in streptomyces globisporus are clustered with the caga gene that encodes the c-1027 apoprotein Antimicrobial Agents and Chemotherapy  2000 44:382-392  DOI:10.1128/aac.44.2.382-392.2000  PMID:10639366
    • Shen, B. Biosynthesis of aromatic polyketides Biosynthesis: Aromatic Polyketides, Isoprenoids, Alkaloids  2000 209:1-51
    • Du, L. C., Shen, B. Identification and characterization of a type ii peptidyl carrier protein from the bleomycin producer streptomyces verticillus atcc 15003 Chemistry & Biology  1999 6:507-517  DOI:10.1016/s1074-5521(99)80083-0  PMID:10421758
    • Shen, B., Du, L. C., Sanchez, C., Chen, M., Edwards, D. J. Bleomycin biosynthesis in streptomyces verticillus atcc15003: A model of hybrid peptide and polyketide biosynthesis Bioorganic Chemistry  1999 27:155-171  DOI:10.1006/bioo.1998.1131
    • Thorson, J. S., Shen, B., Whitwam, R. E., Liu, W., Li, Y., Ahlert, J. Enediyne biosynthesis and self-resistance: A progress report Bioorganic Chemistry  1999 27:172-188  DOI:10.1006/bioo.1998.1122
    • Shen, B., Hutchinson, C. R. Deciphering the mechanism for the assembly of aromatic polyketides by a bacterial polyketide synthase Proceedings of the National Academy of Sciences of the United States of America  1996 93:6600-6604  DOI:10.1073/pnas.93.13.6600  PMID:8692863
    • Summers, R. G., Ali, A., Shen, B., Wessel, W. A., Hutchinson, C. R. Malonyl-coenzyme a-acyl carrier protein acyltransferase of streptomyces-glaucescens - a possible link between fatty-acid and polyketide biosynthesis Biochemistry  1995 34:9389-9402  DOI:10.1021/bi00029a015  PMID:7626609
    • Shen, B., Summers, R. G., Wendtpienkowski, E., Hutchinson, C. R. The streptomyces-glaucescens tcmkl polyketide synthase and tcmn polyketide cyclase genes govern the size and shape of aromatic polyketides Journal of the American Chemical Society  1995 117:6811-6821  DOI:10.1021/ja00131a002
    • Shen, B., Hutchinson, C. R. Triple hydroxylation of tetracenomycin-a2 to tetracenomycin-c in streptomyces-glaucescens - overexpression of the tcmg gene in streptomyces-lividans and characterization of the tetracenomycin-a2 oxygenase Journal of Biological Chemistry  1994 269:30726-30733  PMID:7982994
    • Shen, B., Hutchinson, C. R. Enzymatic-synthesis of a bacterial polyketide from acetyl and malonyl coenzyme-a Science  1993 262:1535-1540  DOI:10.1126/science.8248801  PMID:8248801
    • Shen, B., Hutchinson, C. R. Tetracenomycin-f2 cyclase - intramolecular aldol condensation in the biosynthesis of tetracenomycin-c in streptomyces-glaucescens Biochemistry  1993 32:11149-11154  DOI:10.1021/bi00092a026  PMID:8218177
    • Shen, B., Nakayama, H., Hutchinson, C. R. Isolation and structural elucidation of tetracenomycin-f2 and tetracenomycin-f1 - early intermediates in the biosynthesis of tetracenomycin-c in streptomyces-glaucescens Journal of Natural Products  1993 56:1288-1293  DOI:10.1021/np50098a013  PMID:8229013
    • Shen, B., Hutchinson, C. R. Tetracenomycin f1-monooxygenase - oxidation of a naphthacenone to a naphthacenequinone in the biosynthesis of tetracenomycin-c in streptomyces-glaucescens Biochemistry  1993 32:6656-6663  DOI:10.1021/bi00077a019  PMID:8329392
    • Shen, B., Summers, R. G., Gramajo, H., Bibb, M. J., Hutchinson, C. R. Purification and characterization of the acyl carrier protein of the streptomyces-glaucescens tetracenomycin-c polyketide synthase Journal of Bacteriology  1992 174:3818-3821  PMID:1592832  PMCID:PMC206074
    • Hutchinson, C. R., Decker, H., Guilfoile, P., Shen, B., Summers, R., Wendt-Pienkowski, E., Wessel, B. Polyketide synthases: enzyme complexes and multifunctional proteins directing the biosynthesis of bacterial metabolites from fatty acids Environmental Science Research  1992 44:3-10
    • Shen, B., Gould, S. J. Opposite facial specificity for 2 hydroquinone epoxidases - (3-si,4-re)-2,5-dihydroxyacetanilide epoxidase from streptomyces ll-c10037 and (3-re,4-si)-2,5-dihydroxyacetanilide epoxidase from streptomyces mpp-3051 Biochemistry  1991 30:8936-8944  DOI:10.1021/bi00101a004  PMID:1892811
    • Gould, S. J., Shen, B. Epoxyquinones from 2,5-dihydroxyacetanilide - opposite facial specificity in the epoxidation by enzymes from streptomyces ll-c10037 and streptomyces mpp 3051 Journal of the American Chemical Society  1991 113:684-686  DOI:10.1021/ja00002a052
    • Shen, B., Whittle, Y. G., Gould, S. J., Keszler, D. A. Structure and absolute stereochemistry of the epoxyquinol ll-c10037-alpha and related metabolites from streptomyces ll-c10037 Journal of Organic Chemistry  1990 55:4422-4426  DOI:10.1021/jo00301a039
    • Gould, S. J., Shen, B., Whittle, Y. G. Biosynthesis of antibiotic ll-c10037-alpha - the steps beyond 3-hydroxyanthranilic acid Journal of the American Chemical Society  1989 111:7932-7938  DOI:10.1021/ja00202a039
    • Liu, C., Chen, Q., Yu, Z., Shen, B. Mordenite-​catalyzed three-​phase hydration of alpha-​pinene: product distribution, kinetics and reaction mechanism Acta Chimica Sinica  1986 44:545-550

featured in

  • Scripps Research Appoints Noted Chemist to Florida Faculty  Newsletter
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Research

research overview

  • Microorganisms produce a large variety of biologically active substances representing a vast diversity of fascinating molecular architecture not available in any other systems. Our research centers on the chemistry, biochemistry and genetics of the biosynthesis of these secondary metabolites. Blending organic chemistry, biochemistry, and molecular biology, we take a multidisciplinary approach to study the secondary metabolism by asking the following questions: what reactions are available in nature, what are the enzymatic mechanisms of these reactions, how are these reactions linked to produce complex structures, what are the regulatory mechanisms of these pathways, and, ultimately, how can we manipulate nature's biosynthetic machinery for the discovery and development of new drugs. Members of our group gain broad training spanning organic chemistry, biochemistry, microbiology and molecular biology, a qualification that is becoming essential for the modern bioorganic chemists who seek career opportunity in both academia and pharmaceutical and biotechnology industry.

    Current research projects include: (i) cloning and characterization of novel natural product biosynthetic gene clusters and machineries, (ii) discovery and elucidation of novel enzymes, biochemistry, and mechanism of catalysis, (iii) engineering of natural product structure diversity by combinatorial biosynthesis methods for drug discovery and development, (iv) expression of natural product biosynthetic gene clusters in heterologous hosts for natural product production and development of new strategies for combinatorial biosynthesis, and (v) microbial natural product isolation and structural elucidation for anticancer and antiinfective drug discovery.

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Teaching

advisees

  • graduate advising relationship

    • Adhikari, Ajeeth, Ph.D.  candidate, 2016 -
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Background

education and training

  • Ph.D. in Organic Chemistry and Biochemistry, Oregon State University 1991
  • M.S. in Chemistry, Chinese Academy of Sciences 1984
  • B.S. in Chemistry, Hangzhou University 1982

awards and honors

  • Fellow of the American Academy of Arts and Sciences, conferred by American Academy of Arts & Sciences, 2011
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Contact

full name

  • Ben Shen

geographic location

  • Scripps Florida 
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Identity

ORCID iD

  • ORCID iD http://orcid.org/0000-0002-9750-5982

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