Shen, Ben

Faculty Member

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

Drug Discovery (UMLS)

Contact

shenb@scripps.edu

Websites

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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
- Lohman, J. R., Shen, B. The LnmK Bifunctional Acyltransferase/Decarboxylase Specifying (2R)-Methylmalonyl-CoA and Employing Substrate-Assisted Catalysis for Polyketide Biosynthesis Biochemistry 2020 59:CP3-4147 DOI:10.1021/acs.biochem.0c00749 PMID:33095002
- 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
- Estevez, B., Kim, K., Delaney, M. K., Stojanovic-Terpo, A., Shen, B., Ruan, C., Cho, J., Ruggeri, Z. M., Du, X. Signaling-mediated cooperativity between glycoprotein Ib-IX and protease-activated receptors in thrombin-induced platelet activation Blood 2016 127:626-636 DOI:10.1182/blood-2015-04-638387 PMID:26585954 PMCID:PMC4742550
- Huang, Y., Tang, G. L., Pan, G., Chang, C. Y., Shen, B. Characterization of the ketosynthase and acyl carrier protein domains at the Lnml nonribosomal peptide synthetase-polyketide synthase interface for leinamycin biosynthesis Organic Letters 2016 18:4288-4291 DOI:10.1021/acs.orglett.6b02033 PMID:27541042 PMCID:PMC5013926
- Shen, B. A new golden age of natural products drug discovery Cell 2015 163:1297-1300 DOI:10.1016/j.cell.2015.11.031 PMID:26638061 PMCID:PMC5070666
- Rudolf, J. D., Bigelow, L., Chang, C., Cuff, M. E., Lohman, J. R., Chang, C. Y., Ma, M., Yang, D., Clancy, S., Babnigg, G., Joachimiak, A., Phillips Jr., G. N., et al. Crystal structure of the zorbamycin-binding protein ZbmA, the primary self-resistance element in Streptomyces flavoviridis ATCC21892 Biochemistry 2015 54:6842-6851 DOI:10.1021/acs.biochem.5b01008 PMID:26512730 PMCID:PMC4809751
- Liu, T., Ma, M., Ge, H. M., Yang, C., Cleveland, J., Shen, B. Synthesis and evaluation of 8,4 '-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin Bioorganic & Medicinal Chemistry Letters 2015 25:4899-4902 DOI:10.1016/j.bmcl.2015.05.078 PMID:26071634 PMCID:PMC4607584
- Liu, T., Ma, M., Ge, H. M., Yang, C., Cleveland, J., Shen, B. Synthesis and evaluation of 8,4'-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin Bioorganic & Medicinal Chemistry Letters 2015 DOI:10.1016/j.bmcl.2015.05.078 PMID:26071634 PMCID:PMC4607584
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- Huang, S. X., Zhao, L. X., Tang, S. K., Jiang, C. L., Duan, Y. W., Shen, B. Erythronolides h and i, new erythromycin congeners from a new halophilic actinomycete actinopolyspora sp yim90600 Organic Letters 2009 11:1353-1356 DOI:10.1021/ol900143j PMID:19228040 PMCID:PMC4123550
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- Ju, J. H., Rajski, S. R., Lim, S. K., Seo, J. W., Peters, N. R., Hoffmann, F. M., Shen, B. Lactimidomycin, iso-migrastatin and related glutarimide-containing 12-membered macrolides are extremely potent inhibitors of cell migration Journal of the American Chemical Society 2009 131:1370-1371 DOI:10.1021/ja808462p PMID:19132897 PMCID:PMC2651819
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- Galm, U., Wendt-Pienkowski, E., Wang, L. Y., George, N. P., Oh, T. J., Yi, F., Tao, M. F., Coughlin, J. M., Shen, B. The biosynthetic gene cluster of zorbamycin, a member of the bleomycin family of antitumor antibiotics, from streptomyces flavoviridis atcc 21892 Molecular Biosystems 2009 5:77-90 DOI:10.1039/b814075h PMID:19081934 PMCID:PMC3086045
- Rajski, S. R., Shen, B. The role of evolution in the discovery of new drugs and chemicals ACS Symposium Series 2009 1025:205-232 DOI:10.1021/bk-2009-1025.ch011
- Ju, J. H., Rajski, S. R., Lim, S. K., Seo, J. W., Peters, N. R., Hoffmann, F. M., Shen, B. Evaluation of new migrastatin and dorrigocin congeners unveils cell migration inhibitors with dramatically improved potency Bioorganic & Medicinal Chemistry Letters 2008 18:5951-5954 DOI:10.1016/j.bmcl.2008.07.072 PMID:18684620 PMCID:PMC2585373
- Li, W. L., Ju, J. H., Rajski, S. R., Osada, H., Shen, B. Characterization of the tautomycin biosynthetic gene cluster from streptomyces spiroverticillatus unveiling new insights into dialkylmaleic anhydride and polyketide biosynthesis Journal of Biological Chemistry 2008 283:28607-28617 DOI:10.1074/jbc.M804279200 PMID:18708355 PMCID:PMC2568922
- Galm, U., Wang, L. Y., Wendt-Pienkowski, E., Yang, R. Y., Liu, W., Tao, M. F., Coughlin, J. M., Shen, B. In vivo manipulation of the bleomycin biosynthetic gene cluster in streptomyces verticillus atcc15003 revealing new insights into its biosynthetic pathway Journal of Biological Chemistry 2008 283:28236-28245 DOI:10.1074/jbc.M804971200 PMID:18697737 PMCID:PMC2568937
- Chen, Y., Wendt-Pienkowski, E., Shen, B. Identification and utility of fdmr1 as a streptomyces antibiotic regulatory protein activator for fredericamycin production in streptomyces griseus atcc 49344 and heterologous hosts Journal of Bacteriology 2008 190:5587-5596 DOI:10.1128/jb.00592-08 PMID:18556785 PMCID:PMC2519381
- Luo, Y. G., Lin, S. J., Zhang, J., Cooke, H. A., Bruner, S. D., Shen, B. Regiospecific o-methylation of naphthoic acids catalyzed by ncsb1, an o-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin Journal of Biological Chemistry 2008 283:14694-14702 DOI:10.1074/jbc.M802206200 PMID:18387946 PMCID:PMC2386921
- Lin, S. J., Van Lanen, S. G., Shen, B. Characterization of the two-component, fad-dependent monooxygenase sgcc that requires carrier protein-tethered substrates for the biosynthesis of the enediyne antitumor antibiotic c-1027 Journal of the American Chemical Society 2008 130:6616-6623 DOI:10.1021/ja710601d PMID:18426211
- Jiang, H., Zirkle, R., Metz, J. G., Braun, L., Richter, L., Van Lanen, S. G., Shen, B. The role of tandem acyl carrier protein domains in polyunsaturated fatty acid biosynthesis Journal of the American Chemical Society 2008 130:6336-6337 DOI:10.1021/ja801911t PMID:18444614
- Montavon, T. J., Christianson, C. V., Festin, G. M., Shen, B., Bruner, S. D. Design and characterization of mechanism-based inhibitors for the tyrosine aminomutase sgtam Bioorganic & Medicinal Chemistry Letters 2008 18:3099-3102 DOI:10.1016/j.bmcl.2007.11.046 PMID:18078753
- Song, D. F., Coughlin, J., Ju, J. H., Zhou, X. F., Shen, B., Zhao, C. H., Deng, Z. X. Alternative method for site-directed mutagenesis of complex polyketide synthase in streptomyces albus ja3453 Acta Biochimica et Biophysica Sinica 2008 40:319-326 DOI:10.1111/j.1745-7270.2008.00408.x PMID:18401530
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- Chen, Y. H., Luo, Y. G., Ju, J. H., Wendt-Pienkowski, E., Rajski, S. R., Shen, B. Identification of fredericamycin e from streptomyces griseus: Insights into fredericamycin a biosynthesis highlighting carbaspirocycle formation Journal of Natural Products 2008 71:431-437 DOI:10.1021/np070664n PMID:18232659
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- Tang, G. L., Cheng, Y. Q., Shen, B. Chain initiation in the leinamycin-producing hybrid nonribosomal peptide/polyketide synthetase from streptomyces atroolivaceus s-140 - discrete, monofunctional adenylation enzyme and peptidyl carrier protein that directly load d-alanine Journal of Biological Chemistry 2007 282:20273-20282 DOI:10.1074/jbc.M702814200 PMID:17502372
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- Christianson, C. V., Montavon, T. J., Van Lanen, S. G., Shen, B., Bruner, S. D. The structure of l-tyrosine 2,3-aminomutase from the c-1027 enediyne antitumor antibiotic biosynthetic pathway Biochemistry 2007 46:7205-7214 DOI:10.1021/bi7003685 PMID:17516659
- Guan, C. H., Ju, J. J., Borlee, B. R., Williamson, L. L., Shen, B., Raffa, K. F., Handelsman, J. Signal mimics derived from a metagenomic analysis of the gypsy moth gut microbiota Applied and Environmental Microbiology 2007 73:3669-3676 DOI:10.1128/aem.02617-06 PMID:17435000
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- 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

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