Ben Shen

Ben Shen, Ph.D.

Professor

Department: SR-CHEM-SHEN LAB
Business Phone: (561) 228-2000
Business Email: ben.shen@ufl.edu

About Ben Shen

Related Links:
Additional Positions:
Professor (Joint Appointment), Molecular Therapeutics
2011 – 2017 · Scripps Research
Principal Investigator, NCI UW National Cooperative Drug Discovery Group
2005 – 2010 · University of Wisconsin-Madison
School of Pharmacy and Department of Chemistry
2004 – 2010 · University of Wisconsin-Madison
Charles M. Johnson Distinguished Chair, School of Pharmacy
2004 – 2010 · University of Wisconsin-Madison
Associate Professor, School of Pharmacy and Department of Chemistry
2001 – 2003 · University of Wisconsin-Madison
Assistant Professor, Department of Chemistry
1995 – 2001 · University of California, Davis
Postdoctoral Research Associate
1991 – 1995 · University of Wisconsin-Madison

Accomplishments

Fellow
2021 · American Society of Pharmacognosy
Guest Co-Editor
2021 · J. Ind. Microbiol. Biotechnol. March-April special issue on Natural Product Discovery and Development in the Genomic Era: 2021
Outstanding Mentor Award
2020 · Society of Research Fellows, TSRI, Jupiter, FL
Charles Thom Award
2018 · Society of Industrial Microbiology and Biotechnology
Editor
2017-2022 · J. Ind. Microbiol. Biotechnol.
Promega Biotechnology Research Award
2015 · American Society for Microbiology
Guest Co-Editor
2012 · Curr. Opinion Chem. Biol. April issue on Biocatalysis and Biotransformation
Fellow
2011 · American Academy of Microbiology
Fellow
2011 · American Association for the Advancement of Science
Guest Co-Editor
2011 · J. Antibiot. January issue in memory of C. Richard Hutchinson
Member, Editorial Board
2009-2022 · J. Antibiot.
Associate Editor
2006-2022 · Acta Microbiologica Sinica
Member, Advisory Board
2005-2017 · Mol. BioSyst.
Member, Editorial Advisory Board
2003-2017 · J. Nat. Prod.
Member
2002-2016 · Editorial Board of J. Ind. Microbiol. Biotechnol.
Jack L. Beal Award
2002 · American Society of Pharmacognosy
Independent Scientist Award
2001-2006 · National Institutes of Health
Matt Suffness Award
2000 · American Society of Pharmacognosy
CAREER Award
1998-2003 · NSF
Searle Scholar
1997-2000 · Searle Scholars Program
FIRST Award
1996-2001 · National Institutes of Health

Research Profile

Natural Product Biosynthesis, Engineering, and Drug Discovery. 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 leverage a large microbial strain collection and develop enabling genome mining and synthetic biology technologies for natural product discovery and production, and 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 (http://www.scripps.edu/shen/).

Natural Products Discovery Center at Scripps Research. Natural products are significantly underrepresented in current small molecule libraries. The current Natural Products Library (NPL) at Scripps Research’s Natural Product Discovery Center consists of: (i) purified natural products with fully assigned structures, (b) MPLC (on C-18 semipreparative column) fractions, and (c) crude extracts. The NPL is presented in 384-well format with all materials dissolved in DMSO (1 mM for pure compounds and 50 mg/mL for fractions and extracts), compatible with most of the HTS platforms. The NPL currently available for screening includes: (a) ~600 pure natural products, (b) ~53,500 MPLC fractions, (c) ~205,000 crude extracts. The NPL provides an unprecedented molecular diversity to screen emerging targets for drug leads, and selected members of the NPL serves as outstanding small molecule probes to interrogate biology. Central to the Natural Products Discovery Center is the large microbial strain collection, containing a total of 217,352 bacterial and fungal strains, of which 62,328 are actinobacteria, 14,465 other bacteria, 92,225 fungi, and 48,334 unidentified (bacteria or fungi). Promising leads could therefore be produced in sufficient quantities by microbial fermentation for follow up studies and, ultimately, clinical development.

Open Researcher and Contributor ID (ORCID)

0000-0002-9750-5982

Publications

2022
Functional Characterization of Cytochrome P450 Hydroxylase YpmL in Yangpumicin A Biosynthesis and Its Application for Anthraquinone-Fused Enediyne Structural Diversification
Organic Letters. 24(5):1219-1223 [DOI] 10.1021/acs.orglett.2c00009.
2022
MIO-containing aminomutases for α- to β-amino acids
Trends in Chemistry. 4(1):91-92 [DOI] 10.1016/j.trechm.2021.09.007.
2022
Rational Approach to Identify RNA Targets of Natural Products Enables Identification of Nocathiacin as an Inhibitor of an Oncogenic RNA
ACS Chemical Biology. 17(2):474-482 [DOI] 10.1021/acschembio.1c00952.
2021
Challenges and Opportunities to Develop Enediyne Natural Products as Payloads for Antibody-Drug Conjugates.
Antibody therapeutics. 4(1):1-15 [DOI] 10.1093/abt/tbab001. [PMID] 33554043.
2021
Cryptic Sulfur Incorporation in Thioangucycline Biosynthesis
Angewandte Chemie International Edition. 60(13):7140-7147 [DOI] 10.1002/anie.202015570. [PMID] 33465268.
2021
Cryptic Sulfur Incorporation in Thioangucycline Biosynthesis
Angewandte Chemie. 133(13):7216-7223 [DOI] 10.1002/ange.202015570.
2021
Cytochrome P450 Hydroxylase TnmL Catalyzing Sequential Hydroxylation with an Additional Proofreading Activity in Tiancimycin Biosynthesis
ACS Chemical Biology. 16(7):1172-1178 [DOI] 10.1021/acschembio.1c00365. [PMID] 34138533.
2021
Discovery of ammosesters by mining the Streptomyces uncialis DCA2648 genome revealing new insight into ammosamide biosynthesis
Journal of Industrial Microbiology and Biotechnology. 48(3-4) [DOI] 10.1093/jimb/kuab027. [PMID] 33982054.
2021
Introduction to the special issue: “Natural Product Discovery and Development in the Genomic Era: 2021”
Journal of Industrial Microbiology and Biotechnology. 48(3-4) [DOI] 10.1093/jimb/kuab030. [PMID] 33904896.
2021
PtmC Catalyzes the Final Step of Thioplatensimycin, Thioplatencin, and Thioplatensilin Biosynthesis and Expands the Scope of Arylamine N-Acetyltransferases
ACS Chemical Biology. 16(1):96-105 [DOI] 10.1021/acschembio.0c00773. [PMID] 33314918.
2021
Semisynthesis and Biological Evaluation of Platencin Thioether Derivatives: Dual FabF and FabH Inhibitors against MRSA
ACS Medicinal Chemistry Letters. 12(3):433-442 [DOI] 10.1021/acsmedchemlett.0c00653. [PMID] 33738071.
2021
Submerged fermentation of Streptomyces uncialis providing a biotechnology platform for uncialamycin biosynthesis, engineering, and production
Journal of Industrial Microbiology and Biotechnology. 48(3-4) [DOI] 10.1093/jimb/kuab025. [PMID] 33739406.
2021
Thiocysteine lyases as polyketide synthase domains installing hydropersulfide into natural products and a hydropersulfide methyltransferase
Nature Communications. 12(1) [DOI] 10.1038/s41467-021-25798-8. [PMID] 34584078.
2020
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. 63(15):8432-8441 [DOI] 10.1021/acs.jmedchem.0c00799. [PMID] 32658465.
2020
Divergent synthesis of complex diterpenes through a hybrid oxidative approach
Science. 369(6505):799-806 [DOI] 10.1126/science.abb8271. [PMID] 32792393.
2020
Platensimycin-Encapsulated Liposomes or Micelles as Biosafe Nanoantibiotics Exhibited Strong Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus Infection in Mice
Molecular Pharmaceutics. 17(7):2451-2462 [DOI] 10.1021/acs.molpharmaceut.0c00194.
2020
Platensimycin-Encapsulated Poly(lactic-co-glycolic acid) and Poly(amidoamine) Dendrimers Nanoparticles with Enhanced Anti-Staphylococcal Activity in Vivo
Bioconjugate Chemistry. 31(5):1425-1437 [DOI] 10.1021/acs.bioconjchem.0c00121.
2020
Targeting Bacterial Genomes for Natural Product Discovery
Trends in Pharmacological Sciences. 41(1):13-26 [DOI] 10.1016/j.tips.2019.11.002. [PMID] 31822352.
2020
The Isolation of Pyrroloformamide Congeners and Characterization of Their Biosynthetic Gene Cluster
Journal of Natural Products. 83(2):202-209 [DOI] 10.1021/acs.jnatprod.9b00321. [PMID] 32049520.
2020
The LnmK Bifunctional Acyltransferase/Decarboxylase Specifying (2R)-Methylmalonyl-CoA and Employing Substrate-Assisted Catalysis for Polyketide Biosynthesis
Biochemistry. 59(43):4143-4147 [DOI] 10.1021/acs.biochem.0c00749. [PMID] 33095002.
2019
A 3-hydroxy-3-methylglutaryl-CoA synthase-based probe for the discovery of the acyltransferase-less type I polyketide synthases.
Environmental microbiology. 21(11):4270-4282 [DOI] 10.1111/1462-2920.14787. [PMID] 31435987.
2019
Challenges and opportunities for natural product discovery, production, and engineering in native producers versus heterologous hosts.
Journal of industrial microbiology & biotechnology. 46(3-4):433-444 [DOI] 10.1007/s10295-018-2094-5. [PMID] 30426283.
2019
Characterization and Crystal Structure of a Nonheme Diiron Monooxygenase Involved in Platensimycin and Platencin Biosynthesis
Journal of the American Chemical Society. 141(31):12406-12412 [DOI] 10.1021/jacs.9b06183. [PMID] 31291107.
2019
Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research
Natural Product Reports. 36(1):248-249 [DOI] 10.1039/c8np90041h. [PMID] 30468235.
2019
Cryptic and Stereospecific Hydroxylation, Oxidation, and Reduction in Platensimycin and Platencin Biosynthesis
Journal of the American Chemical Society. 141(9):4043-4050 [DOI] 10.1021/jacs.8b13452. [PMID] 30735041.
2019
Discovery of Kirromycins with Anti-Wolbachia Activity from Streptomyces sp. CB00686
ACS Chemical Biology. 14(6):1174-1182 [DOI] 10.1021/acschembio.9b00086.
2019
Evaluation of Platensimycin and Platensimycin-Inspired Thioether Analogues against Methicillin-Resistant Staphylococcus aureus in Topical and Systemic Infection Mouse Models
Molecular Pharmaceutics. 16(7):3065-3071 [DOI] 10.1021/acs.molpharmaceut.9b00293. [PMID] 31244223.
2019
Late-Stage Functionalization of Platensimycin Leading to Multiple Analogues with Improved Antibacterial Activity in Vitro and in Vivo
Journal of Medicinal Chemistry. 62(14):6682-6693 [DOI] 10.1021/acs.jmedchem.9b00616. [PMID] 31265289.
2019
Leveraging a large microbial strain collection for natural product discovery.
The Journal of biological chemistry. 294(45):16567-16576 [DOI] 10.1074/jbc.REV119.006514. [PMID] 31570525.
2019
Stereoselective functionalization of platensimycin and platencin by sulfa-Michael/aldol reactions
Organic & Biomolecular Chemistry. 17(17):4261-4272 [DOI] 10.1039/c9ob00324j.
2019
The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research
Natural Product Reports. 36(1):35-107 [DOI] 10.1039/c7np00064b. [PMID] 30003207.
2019
Yangpumicins F and G, Enediyne Congeners from Micromonospora yangpuensis DSM 45577
Journal of Natural Products. 82(9):2483-2488 [DOI] 10.1021/acs.jnatprod.9b00229. [PMID] 31490685.
2018
Activities of recombinant human bleomycin hydrolase on bleomycins and engineered analogues revealing new opportunities to overcome bleomycin-induced pulmonary toxicity.
Bioorganic & medicinal chemistry letters. 28(16):2670-2674 [DOI] 10.1016/j.bmcl.2018.04.065. [PMID] 29730026.
2018
Biochemical and Structural Characterization of TtnD, a Prenylated FMN-Dependent Decarboxylase from the Tautomycetin Biosynthetic Pathway
ACS Chemical Biology. 13(9):2728-2738 [DOI] 10.1021/acschembio.8b00673.
2018
Biomimetic Stereoselective Sulfa-Michael Addition Leads to Platensimycin and Platencin Sulfur Analogues against Methicillin-Resistant Staphylococcus aureus
Journal of Natural Products. 81(2):316-322 [DOI] 10.1021/acs.jnatprod.7b00745. [PMID] 29389125.
2018
Biosynthesis of thiocarboxylic acid-containing natural products
Nature Communications. 9(1) [DOI] 10.1038/s41467-018-04747-y. [PMID] 29915173.
2018
Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space
ACS Central Science. 4(12):1727-1741 [DOI] 10.1021/acscentsci.8b00747. [PMID] 30648156.
2018
Comparative Studies of the Biosynthetic Gene Clusters for Anthraquinone-Fused Enediynes Shedding Light into the Tailoring Steps of Tiancimycin Biosynthesis
Organic Letters. 20(18):5918-5921 [DOI] 10.1021/acs.orglett.8b02584. [PMID] 30212211.
2018
Cytochrome P450-Catalyzed Hydroxylation Initiating Ether Formation in Platensimycin Biosynthesis
Journal of the American Chemical Society. 140(39):12349-12353 [DOI] 10.1021/jacs.8b08012. [PMID] 30216060.
2018
Discovery and Characterization of 1-Aminocyclopropane-1-carboxylic Acid Synthase of Bacterial Origin
Journal of the American Chemical Society. 140(49):16957-16961 [DOI] 10.1021/jacs.8b11463.
2018
Discovery of Alternative Producers of the Enediyne Antitumor Antibiotic C-1027 with High Titers
Journal of Natural Products. 81(3):594-599 [DOI] 10.1021/acs.jnatprod.7b01013. [PMID] 29345939.
2018
Discovery of the Tiancilactone Antibiotics by Genome Mining of Atypical Bacterial Type II Diterpene Synthases
ChemBioChem. 19(16):1727-1733 [DOI] 10.1002/cbic.201800285. [PMID] 29806086.
2018
Herbicidins from Streptomyces sp. CB01388 Showing Anti-Cryptosporidium Activity
Journal of Natural Products. 81(4):791-797 [DOI] 10.1021/acs.jnatprod.7b00850.
2018
Huanglongmycin A-C, Cytotoxic Polyketides Biosynthesized by a Putative Type II Polyketide Synthase From Streptomyces sp. CB09001.
Frontiers in chemistry. 6 [DOI] 10.3389/fchem.2018.00254. [PMID] 30013965.
2018
Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme
Nature Chemical Biology. 14(7):730-737 [DOI] 10.1038/s41589-018-0061-0. [PMID] 29867143.
2018
Oxidative activation of leinamycin E1 triggers alkylation of guanine residues in double-stranded DNA
Chemical Communications. 54(3):256-259 [DOI] 10.1039/c7cc08482j.
2018
P450-Catalyzed Tailoring Steps in Leinamycin Biosynthesis Featuring Regio- and Stereoselective Hydroxylations and Substrate Promiscuities
Biochemistry. 57(33):5005-5013 [DOI] 10.1021/acs.biochem.8b00623. [PMID] 30070831.
2018
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. 57(6):1003-1011 [DOI] 10.1021/acs.biochem.7b01219.
2018
Resistance to Enediyne Antitumor Antibiotics by Sequestration.
Cell chemical biology. 25(9):1075-1085.e4 [DOI] 10.1016/j.chembiol.2018.05.012. [PMID] 29937405.
2018
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. 45(3):141-151 [DOI] 10.1007/s10295-018-2014-8. [PMID] 29396746.
2018
Semisynthesis and Biological Evaluation of Platensimycin Analogues with Varying Aminobenzoic Acids.
ChemistrySelect. 3(44):12625-12629 [DOI] 10.1002/slct.201802475. [PMID] 32232122.
2018
Semisynthesis of Platensimycin Derivatives with Antibiotic Activities in Mice via Suzuki–Miyaura Cross-Coupling Reactions
Journal of Medicinal Chemistry. 61(24):11341-11348 [DOI] 10.1021/acs.jmedchem.8b01580. [PMID] 30461269.
2018
Strain improvement by combined UV mutagenesis and ribosome engineering and subsequent fermentation optimization for enhanced 6′-deoxy-bleomycin Z production.
Applied microbiology and biotechnology. 102(4):1651-1661 [DOI] 10.1007/s00253-017-8705-7. [PMID] 29279956.
2018
Structural Insights into the Free-Standing Condensation Enzyme SgcC5 Catalyzing Ester-Bond Formation in the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027
Biochemistry. 57(23):3278-3288 [DOI] 10.1021/acs.biochem.8b00174. [PMID] 29533601.
2018
The discovery and development of microbial bleomycin analogues.
Applied microbiology and biotechnology. 102(16):6791-6798 [DOI] 10.1007/s00253-018-9129-8. [PMID] 29876605.
2018
The genome-wide sequence specificity of DNA cleavage by bleomycin analogues in human cells
Bioorganic & Medicinal Chemistry. 26(14):4168-4178 [DOI] 10.1016/j.bmc.2018.07.006.
2018
The semi-synthesis, biological evaluation and docking analysis of the oxime, hydrazine and hydrazide derivatives of platensimycin
MedChemComm. 9(5):789-794 [DOI] 10.1039/c8md00081f. [PMID] 30108968.
2017
A Facile Semi-Synthetic Approach towards Halogen-Substituted Aminobenzoic Acid Analogues of Platensimycin.
Tetrahedron. 73(6):771-775 [DOI] 10.1016/j.tet.2016.12.059. [PMID] 28626267.
2017
A Long-Range Acting Dehydratase Domain as the Missing Link for C17-Dehydration in Iso-Migrastatin Biosynthesis
Angewandte Chemie International Edition. 56(25):7247-7251 [DOI] 10.1002/anie.201703588. [PMID] 28464455.
2017
A Long-Range Acting Dehydratase Domain as the Missing Link for C17-Dehydration in Iso-Migrastatin Biosynthesis
Angewandte Chemie. 129(25):7353-7357 [DOI] 10.1002/ange.201703588.
2017
Bleomycin analogues preferentially cleave at the transcription start sites of actively transcribed genes in human cells.
The international journal of biochemistry & cell biology. 85:56-65 [DOI] 10.1016/j.biocel.2017.02.001. [PMID] 28167289.
2017
Competition and co-regulation of spirotoamide and tautomycetin biosynthesis in Streptomyces griseochromogenes, and isolation and structural elucidation of spirotoamide C and D.
The Journal of antibiotics. 70(5):710-714 [DOI] 10.1038/ja.2017.13. [PMID] 28196980.
2017
Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis
ACS Omega. 2(8):5159-5169 [DOI] 10.1021/acsomega.7b00933. [PMID] 28884166.
2017
Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function
Natural Product Reports. 34(9):1141-1172 [DOI] 10.1039/c7np00034k. [PMID] 28758170.
2017
Discovery of the leinamycin family of natural products by mining actinobacterial genomes
Proceedings of the National Academy of Sciences. 114(52) [DOI] 10.1073/pnas.1716245115. [PMID] 29229819.
2017
Engineered production and evaluation of 6′-deoxy-tallysomycin H-1 revealing new insights into the structure-activity relationship of the anticancer drug bleomycin.
The Journal of antibiotics. [DOI] 10.1038/ja.2017.93. [PMID] 28831149.
2017
Genome Mining of Micromonospora yangpuensis DSM 45577 as a Producer of an Anthraquinone-Fused Enediyne
Organic Letters. 19(22):6192-6195 [DOI] 10.1021/acs.orglett.7b03120. [PMID] 29086572.
2017
Genome Mining of Streptomyces mobaraensis DSM40847 as a Bleomycin Producer Providing a Biotechnology Platform To Engineer Designer Bleomycin Analogues
Organic Letters. 19(6):1386-1389 [DOI] 10.1021/acs.orglett.7b00283.
2017
Germicidins H-J from Streptomyces sp. CB00361.
The Journal of antibiotics. 70(2):200-203 [DOI] 10.1038/ja.2016.100. [PMID] 27507632.
2017
In vivo instability of platensimycin and platencin: Synthesis and biological evaluation of urea- and carbamate-platensimycin.
Bioorganic & medicinal chemistry. 25(6):1990-1996 [DOI] 10.1016/j.bmc.2017.02.028. [PMID] 28237556.
2017
New isofuranonaphthoquinones and isoindolequinones from Streptomyces sp. CB01883.
The Journal of antibiotics. 70(4):414-422 [DOI] 10.1038/ja.2016.122. [PMID] 27731333.
2017
Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of l-aspartic acid.
The Journal of antibiotics. 70(7):828-831 [DOI] 10.1038/ja.2017.49. [PMID] 28465627.
2017
Platensimycin and platencin: Inspirations for chemistry, biology, enzymology, and medicine.
Biochemical pharmacology. 133:139-151 [DOI] 10.1016/j.bcp.2016.11.013. [PMID] 27865713.
2016
A Mutasynthetic Library of Platensimycin and Platencin Analogues.
Organic letters. 18(18):4606-9 [DOI] 10.1021/acs.orglett.6b02248. [PMID] 27599271.
2016
Antibacterial sulfur-containing platensimycin and platencin congeners from Streptomyces platensis SB12029.
Bioorganic & medicinal chemistry. 24(24):6348-6353 [DOI] 10.1016/j.bmc.2016.04.026. [PMID] 27134119.
2016
Biosynthetic Origin of the Ether Ring in Platensimycin
Journal of the American Chemical Society. 138(51):16711-16721 [DOI] 10.1021/jacs.6b09818. [PMID] 27966343.
2016
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. 100(24):10555-10562 [PMID] 27704182.
2016
Characterization of the Ketosynthase and Acyl Carrier Protein Domains at the LnmI Nonribosomal Peptide Synthetase-Polyketide Synthase Interface for Leinamycin Biosynthesis.
Organic letters. 18(17):4288-91 [DOI] 10.1021/acs.orglett.6b02033. [PMID] 27541042.
2016
Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027.
The Journal of antibiotics. 69(10):731-740 [DOI] 10.1038/ja.2016.88. [PMID] 27406907.
2016
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. 55(36):5142-54 [DOI] 10.1021/acs.biochem.6b00713. [PMID] 27560143.
2016
Engineered production of cancer targeting peptide (CTP)-containing C-1027 in Streptomyces globisporus and biological evaluation.
Bioorganic & medicinal chemistry. 24(17):3887-3892 [DOI] 10.1016/j.bmc.2016.04.017. [PMID] 27094150.
2016
Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery.
Journal of industrial microbiology & biotechnology. 43(2-3):261-76 [DOI] 10.1007/s10295-015-1671-0. [PMID] 26318027.
2016
Overproduction of lactimidomycin by cross-overexpression of genes encoding Streptomyces antibiotic regulatory proteins.
Applied microbiology and biotechnology. 100(5):2267-77 [DOI] 10.1007/s00253-015-7119-7. [PMID] 26552797.
2016
Strain Prioritization and Genome Mining for Enediyne Natural Products.
mBio. 7(6) [DOI] 10.1128/mBio.02104-16. [PMID] 27999165.
2016
Structure of the ent-Copalyl Diphosphate Synthase PtmT2 from Streptomyces platensis CB00739, a Bacterial Type II Diterpene Synthase.
Journal of the American Chemical Society. 138(34):10905-15 [DOI] 10.1021/jacs.6b04317. [PMID] 27490479.
2016
Titer improvement and pilot-scale production of platensimycin from Streptomyces platensis SB12026.
Journal of industrial microbiology & biotechnology. 43(7):1027-35 [DOI] 10.1007/s10295-016-1769-z. [PMID] 27126098.
2016
Zorbamycin has a different DNA sequence selectivity compared with bleomycin and analogues.
Bioorganic & medicinal chemistry. 24(22):6094-6101 [DOI] 10.1016/j.bmc.2016.09.072. [PMID] 27745992.
2015
A genetically amenable platensimycin- and platencin-overproducer as a platform for biosynthetic explorations: a showcase of PtmO4, a long-chain acyl-CoA dehydrogenase.
Molecular bioSystems. 11(10):2717-26 [DOI] 10.1039/c5mb00303b. [PMID] 26055255.
2015
A New Golden Age of Natural Products Drug Discovery.
Cell. 163(6):1297-300 [DOI] 10.1016/j.cell.2015.11.031. [PMID] 26638061.
2015
Adipostatins A-D from Streptomyces sp. 4875 inhibiting Brugia malayi asparaginyl-tRNA synthetase and killing adult Brugia malayi parasites.
The Journal of antibiotics. 68(8):540-2 [DOI] 10.1038/ja.2015.22. [PMID] 25735843.
2015
Angucyclines and Angucyclinones from Streptomyces sp. CB01913 Featuring C-Ring Cleavage and Expansion.
Journal of natural products. 78(10):2471-80 [DOI] 10.1021/acs.jnatprod.5b00601. [PMID] 26335269.
2015
C-S bond cleavage by a polyketide synthase domain.
Proceedings of the National Academy of Sciences of the United States of America. 112(33):10359-64 [DOI] 10.1073/pnas.1508437112. [PMID] 26240335.
2015
Crystal Structure of the Zorbamycin-Binding Protein ZbmA, the Primary Self-Resistance Element in Streptomyces flavoviridis ATCC21892.
Biochemistry. 54(45):6842-51 [DOI] 10.1021/acs.biochem.5b01008. [PMID] 26512730.
2015
Deciphering poxvirus gene expression by RNA sequencing and ribosome profiling.
Journal of virology. 89(13):6874-86 [DOI] 10.1128/JVI.00528-15. [PMID] 25903347.
2015
Enediynes: Exploration of microbial genomics to discover new anticancer drug leads.
Bioorganic & medicinal chemistry letters. 25(1):9-15 [DOI] 10.1016/j.bmcl.2014.11.019. [PMID] 25434000.
2015
Leinamycin E1 acting as an anticancer prodrug activated by reactive oxygen species.
Proceedings of the National Academy of Sciences of the United States of America. 112(27):8278-83 [DOI] 10.1073/pnas.1506761112. [PMID] 26056295.
2015
Minimum Information about a Biosynthetic Gene cluster.
Nature chemical biology. 11(9):625-31 [DOI] 10.1038/nchembio.1890. [PMID] 26284661.
2015
Quantitative profiling of initiating ribosomes in vivo.
Nature methods. 12(2):147-53 [DOI] 10.1038/nmeth.3208. [PMID] 25486063.
2015
Structural and evolutionary relationships of “AT-less” type I polyketide synthase ketosynthases.
Proceedings of the National Academy of Sciences of the United States of America. 112(41):12693-8 [DOI] 10.1073/pnas.1515460112. [PMID] 26420866.
2015
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. 25(21):4899-4902 [DOI] 10.1016/j.bmcl.2015.05.078. [PMID] 26071634.
2014
A proteogenomics approach integrating proteomics and ribosome profiling increases the efficiency of protein identification and enables the discovery of alternative translation start sites.
Proteomics. 14(23-24):2688-98 [DOI] 10.1002/pmic.201400180. [PMID] 25156699.
2014
Biosynthetic potential-based strain prioritization for natural product discovery: a showcase for diterpenoid-producing actinomycetes.
Journal of natural products. 77(2):377-87 [DOI] 10.1021/np401063s. [PMID] 24484381.
2014
BlmB and TlmB provide resistance to the bleomycin family of antitumor antibiotics by N-acetylating metal-free bleomycin, tallysomycin, phleomycin, and zorbamycin.
Biochemistry. 53(44):6901-9 [DOI] 10.1021/bi501121e. [PMID] 25299801.
2014
Comparative characterization of the lactimidomycin and iso-migrastatin biosynthetic machineries revealing unusual features for acyltransferase-less type I polyketide synthases and providing an opportunity to engineer new analogues.
Biochemistry. 53(49):7854-65 [DOI] 10.1021/bi501396v. [PMID] 25405956.
2014
Cycloheximide and actiphenol production in Streptomyces sp. YIM56141 governed by single biosynthetic machinery featuring an acyltransferase-less type I polyketide synthase.
Organic letters. 16(11):3072-5 [DOI] 10.1021/ol501179w. [PMID] 24815182.
2014
Enediyne polyketide synthases stereoselectively reduce the β-ketoacyl intermediates to β-D-hydroxyacyl intermediates in enediyne core biosynthesis.
Organic letters. 16(15):3958-61 [DOI] 10.1021/ol501767v. [PMID] 25019332.
2014
Mechanisms of self-resistance in the platensimycin- and platencin-producing Streptomyces platensis MA7327 and MA7339 strains.
Chemistry & biology. 21(3):389-397 [DOI] 10.1016/j.chembiol.2014.01.005. [PMID] 24560608.
2014
Medium optimization of Streptomyces sp. 17944 for tirandamycin B production and isolation and structural elucidation of tirandamycins H, I and J.
The Journal of antibiotics. 67(1):127-32 [DOI] 10.1038/ja.2013.50. [PMID] 23715040.
2014
Strain prioritization for natural product discovery by a high-throughput real-time PCR method.
Journal of natural products. 77(10):2296-303 [DOI] 10.1021/np5006168. [PMID] 25238028.
2014
The radiomimetic enediyne, 20′-deschloro-C-1027 induces inter-strand DNA crosslinks in hypoxic cells and overcomes cytotoxic radioresistance.
DNA repair. 21:165-70 [DOI] 10.1016/j.dnarep.2014.06.001. [PMID] 24986640.
2013
A new member of the 4-methylideneimidazole-5-one-containing aminomutase family from the enediyne kedarcidin biosynthetic pathway.
Proceedings of the National Academy of Sciences of the United States of America. 110(20):8069-74 [DOI] 10.1073/pnas.1304733110. [PMID] 23633564.
2013
Cloning and sequencing of the kedarcidin biosynthetic gene cluster from Streptoalloteichus sp. ATCC 53650 revealing new insights into biosynthesis of the enediyne family of antitumor antibiotics.
Molecular bioSystems. 9(3):478-91 [DOI] 10.1039/c3mb25523a. [PMID] 23360970.
2013
Development of a chemically defined medium for the production of the antibiotic platensimycin by Streptomyces platensis.
Applied microbiology and biotechnology. 97(21):9535-9 [PMID] 24022611.
2013
Isolation and structural elucidation of glucoside congeners of platencin from Streptomyces platensis SB12600.
The Journal of antibiotics. 66(5):291-4 [DOI] 10.1038/ja.2013.1. [PMID] 23361357.
2013
Possible steps of complete disassembly of post-termination complex by yeast eEF3 deduced from inhibition by translocation inhibitors.
Nucleic acids research. 41(1):264-76 [DOI] 10.1093/nar/gks958. [PMID] 23087377.
2013
Post-polyketide synthase steps in iso-migrastatin biosynthesis, featuring tailoring enzymes with broad substrate specificity.
Journal of the American Chemical Society. 135(7):2489-92 [DOI] 10.1021/ja4002635. [PMID] 23394593.
2013
Predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of nine-membered enediyne antitumor antibiotics.
Biochemistry. 52(31):5217-24 [DOI] 10.1021/bi400572a. [PMID] 23844627.
2013
Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature.
Natural product reports. 30(1):108-60 [DOI] 10.1039/c2np20085f. [PMID] 23165928.
2013
Structure of the bifunctional acyltransferase/decarboxylase LnmK from the leinamycin biosynthetic pathway revealing novel activity for a double-hot-dog fold.
Biochemistry. 52(5):902-11 [DOI] 10.1021/bi301652y. [PMID] 23320975.
2012
4-methylideneimidazole-5-one-containing aminomutases in enediyne biosynthesis.
Methods in enzymology. 516:299-319 [DOI] 10.1016/B978-0-12-394291-3.00007-1. [PMID] 23034235.
2012
A designer bleomycin with significantly improved DNA cleavage activity.
Journal of the American Chemical Society. 134(32):13501-9 [DOI] 10.1021/ja3056535. [PMID] 22831455.
2012
Bacterial diterpene synthases: new opportunities for mechanistic enzymology and engineered biosynthesis.
Current opinion in chemical biology. 16(1-2):132-41 [DOI] 10.1016/j.cbpa.2012.03.002. [PMID] 22445175.
2012
Decoding human cytomegalovirus.
Science (New York, N.Y.). 338(6110):1088-93 [DOI] 10.1126/science.1227919. [PMID] 23180859.
2012
Expression of the platencin biosynthetic gene cluster in heterologous hosts yielding new platencin congeners.
Journal of natural products. 75(12):2158-67 [DOI] 10.1021/np3005985. [PMID] 23157615.
2012
Functional characterization of ttnI completing the tailoring steps for tautomycetin biosynthesis in Streptomyces griseochromogenes.
Organic letters. 14(5):1302-5 [DOI] 10.1021/ol300187p. [PMID] 22339318.
2012
Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution.
Proceedings of the National Academy of Sciences of the United States of America. 109(37):E2424-32 [DOI] 10.1073/pnas.1207846109. [PMID] 22927429.
2012
Neaumycin: a new macrolide from Streptomyces sp. NEAU-x211.
Organic letters. 14(5):1254-7 [DOI] 10.1021/ol300074d. [PMID] 22332843.
2012
New WS9326A congeners from Streptomyces sp. 9078 inhibiting Brugia malayi asparaginyl-tRNA synthetase.
Organic letters. 14(18):4946-9 [PMID] 22967068.
2012
Platensimycin and platencin biosynthesis in Streptomyces platensis, showcasing discovery and characterization of novel bacterial diterpene synthases.
Methods in enzymology. 515:163-86 [DOI] 10.1016/B978-0-12-394290-6.00008-2. [PMID] 22999174.
2012
Specificity of the ester bond forming condensation enzyme SgcC5 in C-1027 biosynthesis.
Organic letters. 14(9):2300-3 [DOI] 10.1021/ol300720s. [PMID] 22519717.
2012
Tailoring enzymes acting on carrier protein-tethered substrates in natural product biosynthesis.
Methods in enzymology. 516:321-43 [DOI] 10.1016/B978-0-12-394291-3.00008-3. [PMID] 23034236.
2011
Actinopolysporins A-C and tubercidin as a Pdcd4 stabilizer from the halophilic actinomycete Actinopolyspora erythraea YIM 90600.
Journal of natural products. 74(9):1990-5 [DOI] 10.1021/np200603g. [PMID] 21870828.
2011
Bafilomycins produced by an endophytic actinomycete Streptomyces sp. YIM56209.
The Journal of antibiotics. 64(1):159-62 [DOI] 10.1038/ja.2010.147. [PMID] 21102599.
2011
Characterization of intact antibody-drug conjugates from plasma/serum in vivo by affinity capture capillary liquid chromatography-mass spectrometry.
Analytical biochemistry. 412(1):56-66 [DOI] 10.1016/j.ab.2011.01.004. [PMID] 21216214.
2011
Characterization of the lnmKLM genes unveiling key intermediates for β-alkylation in leinamycin biosynthesis.
Organic letters. 13(3):498-501 [DOI] 10.1021/ol102838y. [PMID] 21192727.
2011
Comparative analysis of the biosynthetic gene clusters and pathways for three structurally related antitumor antibiotics: bleomycin, tallysomycin, and zorbamycin.
Journal of natural products. 74(3):526-36 [DOI] 10.1021/np1008152. [PMID] 21210656.
2011
Cycloheximide and congeners as inhibitors of eukaryotic protein synthesis from endophytic actinomycetes Streptomyces sps. YIM56132 and YIM56141.
The Journal of antibiotics. 64(1):163-6 [DOI] 10.1038/ja.2010.150. [PMID] 21139626.
2011
Dedicated ent-kaurene and ent-atiserene synthases for platensimycin and platencin biosynthesis.
Proceedings of the National Academy of Sciences of the United States of America. 108(33):13498-503 [DOI] 10.1073/pnas.1106919108. [PMID] 21825154.
2011
Improvement of the enediyne antitumor antibiotic C-1027 production by manipulating its biosynthetic pathway regulation in Streptomyces globisporus.
Journal of natural products. 74(3):420-4 [DOI] 10.1021/np100825y. [PMID] 21250756.
2011
Radical-mediated enzymatic carbon chain fragmentation-recombination.
Nature chemical biology. 7(3):154-60 [DOI] 10.1038/nchembio.512. [PMID] 21240261.
2011
SHP2 is a target of the immunosuppressant tautomycetin.
Chemistry & biology. 18(1):101-10 [DOI] 10.1016/j.chembiol.2010.10.015. [PMID] 21276943.
2011
The missing C-17 O-methyltransferase in geldanamycin biosynthesis.
Organic letters. 13(14):3726-9 [DOI] 10.1021/ol201383w. [PMID] 21682254.
2011
Tirandamycins from Streptomyces sp. 17944 inhibiting the parasite Brugia malayi asparagine tRNA synthetase.
Organic letters. 13(8):2034-7 [DOI] 10.1021/ol200420u. [PMID] 21405052.
2011
Titer improvement of iso-migrastatin in selected heterologous Streptomyces hosts and related analysis of mRNA expression by quantitative RT-PCR.
Applied microbiology and biotechnology. 89(6):1709-19 [DOI] 10.1007/s00253-010-3025-1. [PMID] 21132287.
2010
Characterization of FdmV as an amide synthetase for fredericamycin A biosynthesis in Streptomyces griseus ATCC 43944.
The Journal of biological chemistry. 285(50):38853-60 [DOI] 10.1074/jbc.M110.147744. [PMID] 20926388.
2010
Characterization of the epoxide hydrolase NcsF2 from the neocarzinostatin biosynthetic gene cluster.
Organic letters. 12(17):3816-9 [DOI] 10.1021/ol101473t. [PMID] 20704329.
2010
Discovery and total synthesis of a new estrogen receptor heterodimerizing actinopolymorphol A from Actinopolymorpha rutilus.
Organic letters. 12(15):3525-7 [DOI] 10.1021/ol1013526. [PMID] 20593804.
2010
Enediyne antitumor antibiotic maduropeptin biosynthesis featuring a C-methyltransferase that acts on a CoA-tethered aromatic substrate.
Journal of the American Chemical Society. 132(36):12534-6 [DOI] 10.1021/ja1050814. [PMID] 20718468.
2010
Engineering of Streptomyces platensis MA7339 for overproduction of platencin and congeners.
Organic letters. 12(8):1744-7 [DOI] 10.1021/ol100342m. [PMID] 20232845.
2010
Functional characterization of tlmH in Streptoalloteichus hindustanus E465-94 ATCC 31158 unveiling new insight into tallysomycin biosynthesis and affording a novel bleomycin analog.
Molecular bioSystems. 6(2):349-56 [DOI] 10.1039/b918106g. [PMID] 20094654.
2010
Functional characterization of TtnD and TtnF, unveiling new insights into tautomycetin biosynthesis.
Journal of the American Chemical Society. 132(19):6663-71 [DOI] 10.1021/ja9082446. [PMID] 20426415.
2010
Improved production of the tallysomycin H-1 in Streptoalloteichus hindustanus SB8005 strain by fermentation optimization.
Applied microbiology and biotechnology. 86(5):1345-53 [DOI] 10.1007/s00253-009-2406-9. [PMID] 20049429.
2010
Improvement of secondary metabolite production in Streptomyces by manipulating pathway regulation.
Applied microbiology and biotechnology. 86(1):19-25 [DOI] 10.1007/s00253-009-2428-3. [PMID] 20091304.
2010
Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin.
Nature chemical biology. 6(3):209-217 [PMID] 20118940.
2010
Iso-migrastatin Titer Improvement in the Engineered Streptomyces lividans SB11002 Strain by Optimization of Fermentation Conditions.
Biotechnology and bioprocess engineering : BBE. 15(4):664-669 [PMID] 21625393.
2010
Manipulation of pathway regulation in Streptomyces globisporus for overproduction of the enediyne antitumor antibiotic C-1027.
The Journal of antibiotics. 63(8):482-5 [DOI] 10.1038/ja.2010.55. [PMID] 20551990.
2010
Multifaceted modes of action for the glutarimide-containing polyketides revealed.
Chembiochem : a European journal of chemical biology. 11(14):1951-4 [DOI] 10.1002/cbic.201000370. [PMID] 20806307.
2010
NosA catalyzing carboxyl-terminal amide formation in nosiheptide maturation via an enamine dealkylation on the serine-extended precursor peptide.
Journal of the American Chemical Society. 132(46):16324-6 [DOI] 10.1021/ja106571g. [PMID] 21047073.
2010
Oxazolomycin biosynthesis in Streptomyces albus JA3453 featuring an “acyltransferase-less” type I polyketide synthase that incorporates two distinct extender units.
The Journal of biological chemistry. 285(26):20097-108 [DOI] 10.1074/jbc.M109.090092. [PMID] 20406823.
2010
Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes.
Proceedings of the National Academy of Sciences of the United States of America. 107(25):11331-5 [DOI] 10.1073/pnas.1003442107. [PMID] 20534556.
2009
A free-standing condensation enzyme catalyzing ester bond formation in C-1027 biosynthesis.
Proceedings of the National Academy of Sciences of the United States of America. 106(11):4183-8 [DOI] 10.1073/pnas.0808880106. [PMID] 19246381.
2009
Bifunctional acyltransferase/decarboxylase LnmK as the missing link for beta-alkylation in polyketide biosynthesis.
Journal of the American Chemical Society. 131(20):6900-1 [DOI] 10.1021/ja9012134. [PMID] 19405532.
2009
C-1027, a radiomimetic enediyne anticancer drug, preferentially targets hypoxic cells.
Cancer research. 69(2):593-8 [DOI] 10.1158/0008-5472.CAN-08-2753. [PMID] 19147573.
2009
Characterization of SgcE6, the flavin reductase component supporting FAD-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic C-1027.
FEMS microbiology letters. 300(2):237-41 [DOI] 10.1111/j.1574-6968.2009.01802.x. [PMID] 19817865.
2009
Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis.
Journal of the American Chemical Society. 131(45):16410-7 [DOI] 10.1021/ja901242s. [PMID] 19856960.
2009
Characterization of the tautomycetin biosynthetic gene cluster from Streptomyces griseochromogenes provides new insight into dialkylmaleic anhydride biosynthesis.
Journal of natural products. 72(3):450-9 [DOI] 10.1021/np8007478. [PMID] 19191560.
2009
Engineered production of iso-migrastatin in heterologous Streptomyces hosts.
Bioorganic & medicinal chemistry. 17(6):2147-53 [DOI] 10.1016/j.bmc.2008.10.074. [PMID] 19010685.
2009
Engineered Streptomyces platensis strains that overproduce antibiotics platensimycin and platencin.
Antimicrobial agents and chemotherapy. 53(4):1299-304 [DOI] 10.1128/AAC.01358-08. [PMID] 19164156.
2009
Erythronolides H and I, new erythromycin congeners from a new halophilic actinomycete Actinopolyspora sp. YIM90600.
Organic letters. 11(6):1353-6 [DOI] 10.1021/ol900143j. [PMID] 19228040.
2009
Functional characterization of tlmK unveiling unstable carbinolamide intermediates in the tallysomycin biosynthetic pathway.
The Journal of biological chemistry. 284(13):8256-64 [DOI] 10.1074/jbc.M900640200. [PMID] 19189972.
2009
Functional characterization of ttmM unveils new tautomycin analogs and insight into tautomycin biosynthesis and activity.
Organic letters. 11(7):1639-42 [DOI] 10.1021/ol900293j. [PMID] 19281218.
2009
In vivo investigation of the roles of FdmM and FdmM1 in fredericamycin biosynthesis unveiling a new family of oxygenases.
The Journal of biological chemistry. 284(37):24735-43 [DOI] 10.1074/jbc.M109.014191. [PMID] 19620242.
2009
iso-Migrastatin, migrastatin, and dorrigocin production in Streptomyces platensis NRRL 18993 is governed by a single biosynthetic machinery featuring an acyltransferase-less type I polyketide synthase.
The Journal of biological chemistry. 284(43):29746-56 [DOI] 10.1074/jbc.M109.046805. [PMID] 19726666.
2009
Iterative type I polyketide synthases for enediyne core biosynthesis.
Methods in enzymology. 459:97-112 [DOI] 10.1016/S0076-6879(09)04605-9. [PMID] 19362637.
2009
Lactimidomycin, iso-migrastatin and related glutarimide-containing 12-membered macrolides are extremely potent inhibitors of cell migration.
Journal of the American Chemical Society. 131(4):1370-1 [DOI] 10.1021/ja808462p. [PMID] 19132897.
2009
Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.
Biochemistry. 48(40):9590-8 [DOI] 10.1021/bi901257q. [PMID] 19702337.
2009
Nosiheptide biosynthesis featuring a unique indole side ring formation on the characteristic thiopeptide framework.
ACS chemical biology. 4(10):855-64 [DOI] 10.1021/cb900133x. [PMID] 19678698.
2009
Tautomycetin and tautomycin suppress the growth of medullary thyroid cancer cells via inhibition of glycogen synthase kinase-3beta.
Molecular cancer therapeutics. 8(4):914-20 [DOI] 10.1158/1535-7163.MCT-08-0712. [PMID] 19372564.
2009
Tautomycin suppresses growth and neuroendocrine hormone markers in carcinoid cells through activation of the Raf-1 pathway.
American journal of surgery. 197(3):313-9 [DOI] 10.1016/j.amjsurg.2008.10.007. [PMID] 19245907.
2009
The biosynthetic gene cluster of zorbamycin, a member of the bleomycin family of antitumor antibiotics, from Streptomyces flavoviridis ATCC 21892.
Molecular bioSystems. 5(1):77-90 [DOI] 10.1039/b814075h. [PMID] 19081934.
2009
Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications.
Chemistry & biology. 16(2):141-7 [DOI] 10.1016/j.chembiol.2009.01.007. [PMID] 19246004.
2009
Type I polyketide synthases that require discrete acyltransferases.
Methods in enzymology. 459:165-86 [DOI] 10.1016/S0076-6879(09)04608-4. [PMID] 19362640.
2008
A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis.
Proceedings of the National Academy of Sciences of the United States of America. 105(5):1460-5 [DOI] 10.1073/pnas.0711625105. [PMID] 18223152.
2008
Advances in polyketide synthase structure and function.
Current opinion in drug discovery & development. 11(2):186-95 [PMID] 18283606.
2008
Alternative method for site-directed mutagenesis of complex polyketide synthase in Streptomyces albus JA3453.
Acta biochimica et biophysica Sinica. 40(4):319-26 [PMID] 18401530.
2008
Biosynthesis of enediyne antitumor antibiotics.
Current topics in medicinal chemistry. 8(6):448-59 [PMID] 18397168.
2008
Biosynthesis of the enediyne antitumor antibiotic C-1027 involves a new branching point in chorismate metabolism.
Proceedings of the National Academy of Sciences of the United States of America. 105(2):494-9 [DOI] 10.1073/pnas.0708750105. [PMID] 18182490.
2008
Characterization of the tautomycin biosynthetic gene cluster from Streptomyces spiroverticillatus unveiling new insights into dialkylmaleic anhydride and polyketide biosynthesis.
The Journal of biological chemistry. 283(42):28607-17 [DOI] 10.1074/jbc.M804279200. [PMID] 18708355.
2008
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. 130(20):6616-23 [DOI] 10.1021/ja710601d. [PMID] 18426211.
2008
Design and characterization of mechanism-based inhibitors for the tyrosine aminomutase SgTAM.
Bioorganic & medicinal chemistry letters. 18(10):3099-102 [PMID] 18078753.
2008
Evaluation of new migrastatin and dorrigocin congeners unveils cell migration inhibitors with dramatically improved potency.
Bioorganic & medicinal chemistry letters. 18(22):5951-4 [DOI] 10.1016/j.bmcl.2008.07.072. [PMID] 18684620.
2008
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. 190(16):5587-96 [DOI] 10.1128/JB.00592-08. [PMID] 18556785.
2008
Identification of fredericamycin E from Streptomyces griseus: Insights into fredericamycin A biosynthesis highlighting carbaspirocycle formation.
Journal of natural products. 71(3):431-7 [DOI] 10.1021/np070664n. [PMID] 18232659.
2008
In vivo manipulation of the bleomycin biosynthetic gene cluster in Streptomyces verticillus ATCC15003 revealing new insights into its biosynthetic pathway.
The Journal of biological chemistry. 283(42):28236-45 [DOI] 10.1074/jbc.M804971200. [PMID] 18697737.
2008
Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.
The Journal of biological chemistry. 283(21):14694-702 [DOI] 10.1074/jbc.M802206200. [PMID] 18387946.
2008
The role of tandem acyl carrier protein domains in polyunsaturated fatty acid biosynthesis.
Journal of the American Chemical Society. 130(20):6336-7 [DOI] 10.1021/ja801911t. [PMID] 18444614.
2007
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.
The Journal of biological chemistry. 282(28):20273-82 [PMID] 17502372.
2007
Characterization of NcsB2 as a promiscuous naphthoic acid/coenzyme A ligase integral to the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.
Journal of the American Chemical Society. 129(25):7728-9 [PMID] 17539640.
2007
Characterization of the maduropeptin biosynthetic gene cluster from Actinomadura madurae ATCC 39144 supporting a unifying paradigm for enediyne biosynthesis.
Journal of the American Chemical Society. 129(43):13082-94 [PMID] 17918933.
2007
Designer enediynes generate DNA breaks, interstrand cross-links, or both, with concomitant changes in the regulation of DNA damage responses.
Proceedings of the National Academy of Sciences of the United States of America. 104(45):17632-7 [PMID] 17978180.
2007
Glycopeptide antitumor antibiotic zorbamycin from Streptomyces flavoviridis ATCC 21892: strain improvement and structure elucidation.
Journal of natural products. 70(3):402-6 [PMID] 17311457.
2007
Natural product drug discovery: the times have never been better.
Chemistry & biology. 14(10):1098-104 [PMID] 17961822.
2007
New lactimidomycin congeners shed insight into lactimidomycin biosynthesis in Streptomyces amphibiosporus.
Organic letters. 9(25):5183-6 [PMID] 17997563.
2007
Regiospecific chlorination of (S)-beta-tyrosyl-S-carrier protein catalyzed by SgcC3 in the biosynthesis of the enediyne antitumor antibiotic C-1027.
Journal of the American Chemical Society. 129(41):12432-8 [PMID] 17887753.
2007
Signal mimics derived from a metagenomic analysis of the gypsy moth gut microbiota.
Applied and environmental microbiology. 73(11):3669-76 [PMID] 17435000.
2007
Single chemical modifications of the C-1027 enediyne core, a radiomimetic antitumor drug, affect both drug potency and the role of ataxia-telangiectasia mutated in cellular responses to DNA double-strand breaks.
Cancer research. 67(2):773-81 [PMID] 17234789.
2007
The mechanism of MIO-based aminomutases in beta-amino acid biosynthesis.
Journal of the American Chemical Society. 129(51):15744-5 [PMID] 18052279.
2007
The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway.
Biochemistry. 46(24):7205-14 [PMID] 17516659.
2007
The tallysomycin biosynthetic gene cluster from Streptoalloteichus hindustanus E465-94 ATCC 31158 unveiling new insights into the biosynthesis of the bleomycin family of antitumor antibiotics.
Molecular bioSystems. 3(1):60-74 [PMID] 17216057.
2006
A dedicated phosphopantetheinyl transferase for the fredericamycin polyketide synthase from Streptomyces griseus.
The Journal of biological chemistry. 281(40):29660-8 [PMID] 16895912.
2006
Expression of biosynthetic gene clusters in heterologous hosts for natural product production and combinatorial biosynthesis.
Expert opinion on drug discovery. 1(5):409-37 [DOI] 10.1517/17460441.1.5.409. [PMID] 23495943.
2006
Microbial genomics for the improvement of natural product discovery.
Current opinion in microbiology. 9(3):252-60 [PMID] 16651020.
2006
Polyketide chain skipping mechanism in the biosynthesis of the hybrid nonribosomal peptide-polyketide antitumor antibiotic leinamycin in Streptomyces atroolivaceus S-140.
Journal of natural products. 69(3):387-93 [PMID] 16562841.
2006
Substrate specificity of the adenylation enzyme SgcC1 involved in the biosynthesis of the enediyne antitumor antibiotic C-1027.
The Journal of biological chemistry. 281(40):29633-40 [PMID] 16887797.
2006
The bifunctional glyceryl transferase/phosphatase OzmB belonging to the HAD superfamily that diverts 1,3-bisphosphoglycerate into polyketide biosynthesis.
Journal of the American Chemical Society. 128(32):10386-7 [PMID] 16895402.
2006
Thermolysis of isomigrastatin and its congeners via [3,3]-sigmatropic rearrangement: a new route to the synthesis of migrastatin and its analogues.
Organic letters. 8(25):5865-8 [PMID] 17134292.
2006
Utilization of the methoxymalonyl-acyl carrier protein biosynthesis locus for cloning of the tautomycin biosynthetic gene cluster from Streptomyces spiroverticillatus.
Journal of bacteriology. 188(11):4148-52 [PMID] 16707708.
2006
Utilization of the methoxymalonyl-acyl carrier protein biosynthesis locus for cloning the oxazolomycin biosynthetic gene cluster from Streptomyces albus JA3453.
Journal of bacteriology. 188(11):4142-7 [PMID] 16707707.
2005
Antitumor antibiotics: bleomycin, enediynes, and mitomycin.
Chemical reviews. 105(2):739-58 [PMID] 15700963.
2005
Biosynthesis of the beta-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring beta-amino acyl-S-carrier protein intermediates.
Journal of the American Chemical Society. 127(33):11594-5 [PMID] 16104723.
2005
Cloning, sequencing, analysis, and heterologous expression of the fredericamycin biosynthetic gene cluster from Streptomyces griseus.
Journal of the American Chemical Society. 127(47):16442-52 [PMID] 16305230.
2005
Iso-migrastatin congeners from Streptomyces platensis and generation of a glutarimide polyketide library featuring the dorrigocin, lactimidomycin, migrastatin, and NK30424 scaffolds.
Journal of the American Chemical Society. 127(34):11930-1 [PMID] 16117518.
2005
Migrastatin and dorrigocins are shunt metabolites of iso-migrastatin.
Journal of the American Chemical Society. 127(6):1622-3 [PMID] 15700980.
2005
The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases.
Chemistry & biology. 12(3):293-302 [PMID] 15797213.
2004
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. 67(2):206-13 [PMID] 14987060.
2004
Conversion of (2S)-arginine to (2S,3R)-capreomycidine by VioC and VioD from the viomycin biosynthetic pathway of Streptomyces sp. strain ATCC11861.
Chembiochem : a European journal of chemical biology. 5(9):1281-5 [PMID] 15368582.
2004
Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase.
Chemistry & biology. 11(1):33-45 [PMID] 15112993.
2003
A genomics-guided approach for discovering and expressing cryptic metabolic pathways.
Nature biotechnology. 21(2):187-90 [PMID] 12536216.
2003
A novel 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis.
Journal of the American Chemical Society. 125(20):6062-3 [PMID] 12785829.
2003
BlmIII and BlmIV nonribosomal peptide synthetase-catalyzed biosynthesis of the bleomycin bithiazole moiety involving both in cis and in trans aminoacylation.
Biochemistry. 42(32):9731-40 [PMID] 12911315.
2003
Enediyne natural products: biosynthesis and prospect towards engineering novel antitumor agents.
Current medicinal chemistry. 10(21):2317-25 [PMID] 14529344.
2003
Hybrid peptide-polyketide natural products: biosynthesis and prospects towards engineering novel molecules.
Genetic engineering. 25:227-67 [PMID] 15260241.
2003
Kinetic analysis of the 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis.
Biochemistry. 42(43):12708-18 [PMID] 14580219.
2003
Oxidase domains in epothilone and bleomycin biosynthesis: thiazoline to thiazole oxidation during chain elongation.
Biochemistry. 42(32):9722-30 [PMID] 12911314.
2003
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. 100(21):11959-63 [PMID] 14528002.
2003
Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis.
Proceedings of the National Academy of Sciences of the United States of America. 100(6):3149-54 [PMID] 12598647.
2002
Biosynthesis of the enediyne antitumor antibiotic C-1027.
Science (New York, N.Y.). 297(5584):1170-3 [PMID] 12183628.
2002
C-O bond formation by polyketide synthases.
Science (New York, N.Y.). 297(5585):1327-30 [PMID] 12193782.
2002
Cloning and characterization of the bleomycin biosynthetic gene cluster from Streptomyces verticillus ATCC15003.
Journal of natural products. 65(3):422-31 [PMID] 11908996.
2002
Identification and localization of the gene cluster encoding biosynthesis of the antitumor macrolactam leinamycin in Streptomyces atroolivaceus S-140.
Journal of bacteriology. 184(24):7013-24 [PMID] 12446651.
2002
Macrotetrolide biosynthesis: a novel type II polyketide synthase.
Chemical record (New York, N.Y.). 2(6):389-96 [PMID] 12469350.

Grants

Apr 2022 ACTIVE
TrmD-targeting actinobacterial natural products as next generation antibiotics
Role: Principal Investigator
Funding: THOMAS JEFFERSON UNIV via NATL INST OF HLTH NIAID
Apr 2022 ACTIVE
Mining Actinomycetal Genomes for Natural Product Discovery and Biosynthesis
Role: Principal Investigator
Funding: NATL INST OF HLTH NIGMS
Apr 2022 ACTIVE
Novel Enediyne-Based Antibody-Drug Conjugates for Cancers
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Apr 2022 ACTIVE
Characterization of the Thioacid Biosynthetic Machinery and Isolation of a Novel Thioacid Enediyne Natural Product
Role: Other
Funding: NATL INST OF HLTH NIGMS
Apr 2022 – May 2022
Biosynthesis of the Leinamycin Family of Natural Products: Mechanistic Studies and Chemoenzymatic Analog Synthesis
Role: Other
Funding: NATL INST OF HLTH NIGMS

Education

Ph.D. in Organic Chemistry and Biochemistry
1991 · Oregon State University
Master's of Science in Chemistry
1984 · Chinese Academy of Sciences
Bachelor's of Science in Chemistry
1982 · Hangzhou University

Contact Details

Phones:
Business:
(561) 228-2000
Emails:
Business:
ben.shen@ufl.edu
Addresses:
Business Mailing:
120 SCRIPPS WAY
JUPITER FL 33458