Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis

doi:https://doi.org/10.1002/anie.201910241

Title: Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis

Authors:

Wheeler, Ryan; Yu, Xia; Hou, Caixia; Mitra, Prithiba; Chen, Jhong; Min,; Herkules, Frank; Ivanov, Dmitri N.; Tsodikov, Oleg V.; Rohr, Jürgen ^[1]

Kentucky

Publication Date:: 2020-12-11

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:: National Institutes of Health (NIH)

OSTI Identifier:: 1591930

Resource Type:: Journal Article

Journal Name:: Angew. Chem. Int. Ed.

Additional Journal Information:: Journal Volume: 59; Journal Issue: (2) ; 01, 2020

Country of Publication:: United States

Language:: ENGLISH

Citation Formats


                    Wheeler, Ryan, Yu, Xia, Hou, Caixia, Mitra, Prithiba, Chen, Jhong, #8208, Min,, Herkules, Frank, Ivanov, Dmitri N., Tsodikov, Oleg V., Rohr, Jürgen, and Texas-HSC). Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis.  United States: N. p., 2020. 
        Web.  doi:10.1002/anie.201910241.

Copy to clipboard


                    Wheeler, Ryan, Yu, Xia, Hou, Caixia, Mitra, Prithiba, Chen, Jhong, #8208, Min,, Herkules, Frank, Ivanov, Dmitri N., Tsodikov, Oleg V., Rohr, Jürgen, & Texas-HSC). Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis.  United States.  https://doi.org/10.1002/anie.201910241

Copy to clipboard


                    Wheeler, Ryan, Yu, Xia, Hou, Caixia, Mitra, Prithiba, Chen, Jhong, #8208, Min,, Herkules, Frank, Ivanov, Dmitri N., Tsodikov, Oleg V., Rohr, Jürgen, and Texas-HSC). Fri .  
        "Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis".  United States.  https://doi.org/10.1002/anie.201910241.

Copy to clipboard


                    
@article{osti_1591930,

  title        = {Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis},

  author       = {Wheeler, Ryan and Yu, Xia and Hou, Caixia and Mitra, Prithiba and Chen, Jhong and #8208 and Min, and Herkules, Frank and Ivanov, Dmitri N. and Tsodikov, Oleg V. and Rohr, Jürgen and Texas-HSC)},

  abstractNote = {},

  doi          = {10.1002/anie.201910241},

  url          = {https://www.osti.gov/biblio/1591930},
  journal      = {Angew. Chem. Int. Ed.},
number       = (2) ; 01, 2020,

  volume       = 59,

  place        = {United States},

  year         = {2020},

  month        = {12}

}

Copy to clipboard

Journal Article:

https://doi.org/10.1002/anie.201910241

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Works referenced in this record:

Molecular Insight into Substrate Recognition and Catalysis of Baeyer–Villiger Monooxygenase MtmOIV, the Key Frame-Modifying Enzyme in the Biosynthesis of Anticancer Agent Mithramycin
journal, September 2013

Bosserman, Mary A.; Downey, Theresa; Noinaj, Nicholas
ACS Chemical Biology, Vol. 8, Issue 11
https://doi.org/10.1021/cb400399b

Crystal Structure of Baeyer−Villiger Monooxygenase MtmOIV, the Key Enzyme of the Mithramycin Biosynthetic Pathway,
journal, June 2009

Beam, Miranda P.; Bosserman, Mary A.; Noinaj, Nicholas
Biochemistry, Vol. 48, Issue 21
https://doi.org/10.1021/bi8023509

Characterization of Kinetics and Products of the Baeyer−Villiger Oxygenase MtmOIV, The Key Enzyme of the Biosynthetic Pathway toward the Natural Product Anticancer Drug Mithramycin from Streptomyces a rgillaceus
journal, December 2005

Gibson, Miranda; Nur-e-alam, Mohammad; Lipata, Fredilyn
Journal of the American Chemical Society, Vol. 127, Issue 50
https://doi.org/10.1021/ja055750t

The structures of premithramycinone and demethylpremithramycinone, plausible early intermediates of the aureolic acid group antibiotic mithramycin
journal, January 1998

Rohr, Jürgen; Weißbach, Ulrike; Beninga, Claus
Chemical Communications, Issue 3
https://doi.org/10.1039/a707446h

Mithramycin SK, A Novel Antitumor Drug with Improved Therapeutic Index, Mithramycin SA, and Demycarosyl-mithramycin SK: Three New Products Generated in the Mithramycin Producer Streptomyces a rgillaceus through Combinatorial Biosynthesis
journal, May 2003

Remsing, Lily L.; González, Ana M.; Nur-e-Alam, Mohammad
Journal of the American Chemical Society, Vol. 125, Issue 19
https://doi.org/10.1021/ja034162h

Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers
journal, April 2018

Mitra, Prithiba; Eckenrode, Joseph M.; Mandal, Abhisek
Journal of Medicinal Chemistry, Vol. 61, Issue 17
https://doi.org/10.1021/acs.jmedchem.8b01107

Mechanisms of Self-Resistance in the Platensimycin- and Platencin-Producing Streptomyces platensis MA7327 and MA7339 Strains
journal, March 2014

Peterson, Ryan M.; Huang, Tingting; Rudolf, Jeffrey D.
Chemistry & Biology, Vol. 21, Issue 3
https://doi.org/10.1016/j.chembiol.2014.01.005

Production of actinorhodin-related "blue pigments" by Streptomyces coelicolor A3(2).
journal, January 1996

Bystrykh, L. V.; Fernández-Moreno, M. A.; Herrema, J. K.
Journal of bacteriology, Vol. 178, Issue 8
https://doi.org/10.1128/jb.178.8.2238-2244.1996

Solution structure of the mithramycin dimer-DNA complex
journal, July 1993

Sastry, Mallika; Patel, Dinshaw J.
Biochemistry, Vol. 32, Issue 26
https://doi.org/10.1021/bi00077a012

Identification of the Novobiocin Biosynthetic Gene Cluster of Streptomyces spheroides NCIB 11891
journal, May 2000

Steffensky, M.; Muhlenweg, A.; Wang, Z. -X.
Antimicrobial Agents and Chemotherapy, Vol. 44, Issue 5
https://doi.org/10.1128/AAC.44.5.1214-1222.2000

Electrophoresis of Proteins and Protein–Protein Complexes in a Native Agarose Gel
journal, June 2000

Kim, Rosalind; Yokota, Hisao; Kim, Sung-Hou
Analytical Biochemistry, Vol. 282, Issue 1
https://doi.org/10.1006/abio.2000.4598

Identification of an Inhibitor of the EWS-FLI1 Oncogenic Transcription Factor by High-Throughput Screening
journal, June 2011

Grohar, Patrick J.; Woldemichael, Girma M.; Griffin, Laurie B.
JNCI: Journal of the National Cancer Institute, Vol. 103, Issue 12
https://doi.org/10.1093/jnci/djr156

Rapid Communication: Mithramycin Selectively Inhibits Transcription Of G-C Containing DNA
journal, November 1987

Miller, D. M.; Thomas, S. D.; Ray, R.
The American Journal of the Medical Sciences, Vol. 294, Issue 5
https://doi.org/10.1097/00000441-198711000-00015

The Biosynthesis of Aureolic Acid Group Antibiotics
journal, February 1999

Rohr, Jürgen; Méndez, Carmen; Salas, Jose A.
Bioorganic Chemistry, Vol. 27, Issue 1
https://doi.org/10.1006/bioo.1998.1110

Gluconic acid-producing Pseudomonas sp. prevent γ-actinorhodin biosynthesis by Streptomyces coelicolor A3(2)
journal, June 2014

Galet, Justine; Deveau, Aurélie; Hôtel, Laurence
Archives of Microbiology, Vol. 196, Issue 9
https://doi.org/10.1007/s00203-014-1000-4

The Structure of Mithramycin Reinvestigated
journal, January 1999

Wohlert, S. E.; Künzel, E.; Machinek, R.
Journal of Natural Products, Vol. 62, Issue 1
https://doi.org/10.1021/np980355k

Structure of the Cytoplasmic beta Subunit--T1 Assembly of Voltage-Dependent K+ Channels
journal, July 2000

Gulbis, J. M.
Science, Vol. 289, Issue 5476
https://doi.org/10.1126/science.289.5476.123

Functional Coupling between the Kv1.1 Channel and Aldoketoreductase Kvβ1
journal, January 2008

Pan, Yaping; Weng, Jun; Cao, Yu
Journal of Biological Chemistry, Vol. 283, Issue 13
https://doi.org/10.1074/jbc.M709304200

Structures of mithramycin analogues bound to DNA and implications for targeting transcription factor FLI1
journal, September 2016

Hou, Caixia; Weidenbach, Stevi; Cano, Kristin E.
Nucleic Acids Research, Vol. 44, Issue 18
https://doi.org/10.1093/nar/gkw761

Antibiotic resistance is ancient
journal, August 2011

D’Costa, Vanessa M.; King, Christine E.; Kalan, Lindsay
Nature, Vol. 477, Issue 7365
https://doi.org/10.1038/nature10388

Dimerization and DNA recognition rules of mithramycin and its analogues
journal, March 2016

Weidenbach, Stevi; Hou, Caixia; Chen, Jhong-Min
Journal of Inorganic Biochemistry, Vol. 156
https://doi.org/10.1016/j.jinorgbio.2015.12.011

The aldo-keto reductases (AKRs): Overview
journal, June 2015

Penning, Trevor M.
Chemico-Biological Interactions, Vol. 234
https://doi.org/10.1016/j.cbi.2014.09.024

Studies on the structure of olivomycin a and mithramycin by 1H and 13C nuclear magnetic resonance spectroscopy
journal, January 1981

Thiem, Joachim; Meyer, Bernd
Tetrahedron, Vol. 37, Issue 3
https://doi.org/10.1016/S0040-4020(01)92428-7

Mithramycin in the treatment of metastatic ewing's sarcoma
journal, April 1973

Kofman, Sydney; Perlia, Charles P.; Economou, Steven G.
Cancer, Vol. 31, Issue 4
https://doi.org/10.1002/1097-0142(197304)31:4<889::AID-CNCR2820310419>3.0.CO;2-H

Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions
journal, August 2013

Cox, Georgina; Wright, Gerard D.
International Journal of Medical Microbiology, Vol. 303, Issue 6-7
https://doi.org/10.1016/j.ijmm.2013.02.009

Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents
journal, March 1996

Blanco, Gloria; Fu, Hong; Mendez, Carmen
Chemistry & Biology, Vol. 3, Issue 3
https://doi.org/10.1016/S1074-5521(96)90262-8

Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin
journal, January 1999

Prado, Laura; Fernández, Ernestina; Weiβbach, Ulrike
Chemistry & Biology, Vol. 6, Issue 1
https://doi.org/10.1016/S1074-5521(99)80017-9

How mithramycin stereochemistry dictates its structure and DNA binding function
journal, January 2019

Hou, Caixia; Rohr, Jürgen; Parkin, Sean
MedChemComm, Vol. 10, Issue 5
https://doi.org/10.1039/C9MD00100J

Targeting DnaN for tuberculosis therapy using novel griselimycins
journal, June 2015

Kling, A.; Lukat, P.; Almeida, D. V.
Science, Vol. 348, Issue 6239
https://doi.org/10.1126/science.aaa4690

Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel
journal, August 2005

Long, S. B.
Science, Vol. 309, Issue 5736
https://doi.org/10.1126/science.1116269

An ABC transporter is essential for resistance to the antitumor agent mithramycin in the producerStreptomyces argillaceus
journal, July 1996

Fernández, E.; Lombó, F.; Méndez, C.
Molecular and General Genetics MGG, Vol. 251, Issue 6
https://doi.org/10.1007/BF02174118

Similar records in OSTI.GOV collections:

The biosynthesis of cyanogenic glucosides in higher plants. Identification of three hydroxylation steps in the biosynthesis of dhurrin in Sorghum bicolor (L. ) Moench and the involvement of 1-ACI-nitro-2-(p-hydroxyphenyl)ethane as an intermediate

Journal Article Halkier, B A ; Moller, B L - Journal of Biological Chemistry; (USA)

N-Hydroxytyrosine, (E)- and (Z)-p-hydroxyphenyl-acetaldehyde oxime, p-hydroxyphenylacetonitrile, and p-hydroxymandelonitrile are established intermediates in the biosynthesis of the tyrosine-derived cyanogenic glucoside dhurrin. Simultaneous measurements of oxygen consumption and biosynthetic activity using a microsomal enzyme system isolated from etiolated sorghum seedlings demonstrate a requirement for three oxygen molecules in the conversion of tyrosine to p-hydroxymandelonitrile. Two oxygen molecules are consumed in the conversion of tyrosine to (E)-p-hydroxyphenylacetaldehyde oxime, indicating the existence of a previously undetected hydroxylation step in addition to that resulting in the formation of N-hydroxytyrosine. Radioactively labeled 1-nitro-2-(p-hydroxyphenyl)ethane was chemically synthesized and tested as a possible intermediate. Biosynthetic experiments demonstrate thatmore »« less
Discovery of germacrene A synthases in Barnadesia spinosa: The first committed step in sesquiterpene lactone biosynthesis in the basal member of the Asteraceae

Journal Article Nguyen, Trinh-Don ; Faraldos, Juan A. ; Vardakou, Maria ; ... - Biochemical and Biophysical Research Communications

The Andes-endemic Barnadesioideae lineage is the oldest surviving and phylogenetically basal subfamily of the Asteraceae (Compositae), a prolific group of flowering plants with world-wide distribution (∼24,000 species) marked by a rich diversity of sesquiterpene lactones (STLs). Intriguingly, there is no evidence that members of the Barnadesioideae produce STLs, specialized metabolites thought to have contributed to the adaptive success of the Asteraceae family outside South America. The biosynthesis of STLs requires the intimate expression and functional integration of germacrene A synthase (GAS) and germacrene A oxidase (GAO) to sequentially cyclize and oxidize farnesyl diphosphate into the advanced intermediate germacrene A acidmore »« less
https://doi.org/10.1016/J.BBRC.2016.09.165
Molecular Insight into Substrate Recognition and Catalysis of Baeyer-Villiger Monooxygenase MtmOIV, the Key Frame-Modifying Enzyme in the Biosynthesis of Anticancer Agent Mithramycin

Journal Article Bosserman, Mary A. ; Downey, Theresa ; Noinaj, Nicholas ; ... - ACS Chemical Biology

Baeyer–Villiger monooxygenases (BVMOs) have been shown to play key roles for the biosynthesis of important natural products. MtmOIV, a homodimeric FAD- and NADPH-dependent BVMO, catalyzes the key frame-modifying steps of the mithramycin biosynthetic pathway, including an oxidative C–C bond cleavage, by converting its natural substrate premithramycin B into mithramycin DK, the immediate precursor of mithramycin. The drastically improved protein structure of MtmOIV along with the high-resolution structure of MtmOIV in complex with its natural substrate premithramycin B are reported here, revealing previously undetected key residues that are important for substrate recognition and catalysis. Kinetic analyses of selected mutants allowed usmore »« less
https://doi.org/10.1021/cb400399b
Cryptic metasomatism during late-stage lunar magmatism implicated by sulfur in apatite

Journal Article Konecke, Brian A. ; Fiege, Adrian ; Simon, Adam C. ; ... - Geology
https://doi.org/10.1130/G39249.1
Discovery of the cryptic function of terpene cyclases as aromatic prenyltransferases

Journal Article He, Haibing ; Bian, Guangkai ; Herbst-Gervasoni, Corey J. ; ... - Nature Communications

Catalytic versatility is an inherent property of many enzymes. In nature, terpene cyclases comprise the foundation of molecular biodiversity as they generate diverse hydrocarbon scaffolds found in thousands of terpenoid natural products. Here, we report that the catalytic activity of the terpene cyclases AaTPS and FgGS can be switched from cyclase to aromatic prenyltransferase at basic pH to generate prenylindoles. The crystal structures of AaTPS and FgGS provide insights into the catalytic mechanism of this cryptic function. Moreover, aromatic prenyltransferase activity discovered in other terpene cyclases indicates that this cryptic function is broadly conserved among the greater family of terpenemore »« less
https://doi.org/10.1038/s41467-020-17642-2

Full Text Available

Similar Records

Title: Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis

Citation Formats

Molecular Insight into Substrate Recognition and Catalysis of Baeyer–Villiger Monooxygenase MtmOIV, the Key Frame-Modifying Enzyme in the Biosynthesis of Anticancer Agent Mithramycin journal, September 2013

Crystal Structure of Baeyer−Villiger Monooxygenase MtmOIV, the Key Enzyme of the Mithramycin Biosynthetic Pathway, journal, June 2009

Characterization of Kinetics and Products of the Baeyer−Villiger Oxygenase MtmOIV, The Key Enzyme of the Biosynthetic Pathway toward the Natural Product Anticancer Drug Mithramycin from Streptomyces a rgillaceus journal, December 2005

The structures of premithramycinone and demethylpremithramycinone, plausible early intermediates of the aureolic acid group antibiotic mithramycin journal, January 1998

Mithramycin SK, A Novel Antitumor Drug with Improved Therapeutic Index, Mithramycin SA, and Demycarosyl-mithramycin SK: Three New Products Generated in the Mithramycin Producer Streptomyces a rgillaceus through Combinatorial Biosynthesis journal, May 2003

Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers journal, April 2018

Mechanisms of Self-Resistance in the Platensimycin- and Platencin-Producing Streptomyces platensis MA7327 and MA7339 Strains journal, March 2014

Production of actinorhodin-related "blue pigments" by Streptomyces coelicolor A3(2). journal, January 1996

Solution structure of the mithramycin dimer-DNA complex journal, July 1993

Identification of the Novobiocin Biosynthetic Gene Cluster of Streptomyces spheroides NCIB 11891 journal, May 2000

Electrophoresis of Proteins and Protein–Protein Complexes in a Native Agarose Gel journal, June 2000

Identification of an Inhibitor of the EWS-FLI1 Oncogenic Transcription Factor by High-Throughput Screening journal, June 2011

Rapid Communication: Mithramycin Selectively Inhibits Transcription Of G-C Containing DNA journal, November 1987

The Biosynthesis of Aureolic Acid Group Antibiotics journal, February 1999

Gluconic acid-producing Pseudomonas sp. prevent γ-actinorhodin biosynthesis by Streptomyces coelicolor A3(2) journal, June 2014

The Structure of Mithramycin Reinvestigated journal, January 1999

Structure of the Cytoplasmic beta Subunit--T1 Assembly of Voltage-Dependent K+ Channels journal, July 2000

Functional Coupling between the Kv1.1 Channel and Aldoketoreductase Kvβ1 journal, January 2008

Structures of mithramycin analogues bound to DNA and implications for targeting transcription factor FLI1 journal, September 2016

Antibiotic resistance is ancient journal, August 2011

Dimerization and DNA recognition rules of mithramycin and its analogues journal, March 2016

The aldo-keto reductases (AKRs): Overview journal, June 2015

Studies on the structure of olivomycin a and mithramycin by 1H and 13C nuclear magnetic resonance spectroscopy journal, January 1981

Mithramycin in the treatment of metastatic ewing's sarcoma journal, April 1973

Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions journal, August 2013

Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents journal, March 1996

Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin journal, January 1999

How mithramycin stereochemistry dictates its structure and DNA binding function journal, January 2019

Targeting DnaN for tuberculosis therapy using novel griselimycins journal, June 2015

Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel journal, August 2005

An ABC transporter is essential for resistance to the antitumor agent mithramycin in the producerStreptomyces argillaceus journal, July 1996

Molecular Insight into Substrate Recognition and Catalysis of Baeyer–Villiger Monooxygenase MtmOIV, the Key Frame-Modifying Enzyme in the Biosynthesis of Anticancer Agent Mithramycin
journal, September 2013

Crystal Structure of Baeyer−Villiger Monooxygenase MtmOIV, the Key Enzyme of the Mithramycin Biosynthetic Pathway,
journal, June 2009

Characterization of Kinetics and Products of the Baeyer−Villiger Oxygenase MtmOIV, The Key Enzyme of the Biosynthetic Pathway toward the Natural Product Anticancer Drug Mithramycin from Streptomyces a rgillaceus
journal, December 2005

The structures of premithramycinone and demethylpremithramycinone, plausible early intermediates of the aureolic acid group antibiotic mithramycin
journal, January 1998

Mithramycin SK, A Novel Antitumor Drug with Improved Therapeutic Index, Mithramycin SA, and Demycarosyl-mithramycin SK: Three New Products Generated in the Mithramycin Producer Streptomyces a rgillaceus through Combinatorial Biosynthesis
journal, May 2003

Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers
journal, April 2018

Mechanisms of Self-Resistance in the Platensimycin- and Platencin-Producing Streptomyces platensis MA7327 and MA7339 Strains
journal, March 2014

Production of actinorhodin-related "blue pigments" by Streptomyces coelicolor A3(2).
journal, January 1996

Solution structure of the mithramycin dimer-DNA complex
journal, July 1993

Identification of the Novobiocin Biosynthetic Gene Cluster of Streptomyces spheroides NCIB 11891
journal, May 2000

Electrophoresis of Proteins and Protein–Protein Complexes in a Native Agarose Gel
journal, June 2000

Identification of an Inhibitor of the EWS-FLI1 Oncogenic Transcription Factor by High-Throughput Screening
journal, June 2011

Rapid Communication: Mithramycin Selectively Inhibits Transcription Of G-C Containing DNA
journal, November 1987

The Biosynthesis of Aureolic Acid Group Antibiotics
journal, February 1999

Gluconic acid-producing Pseudomonas sp. prevent γ-actinorhodin biosynthesis by Streptomyces coelicolor A3(2)
journal, June 2014

The Structure of Mithramycin Reinvestigated
journal, January 1999

Structure of the Cytoplasmic beta Subunit--T1 Assembly of Voltage-Dependent K+ Channels
journal, July 2000

Functional Coupling between the Kv1.1 Channel and Aldoketoreductase Kvβ1
journal, January 2008

Structures of mithramycin analogues bound to DNA and implications for targeting transcription factor FLI1
journal, September 2016

Antibiotic resistance is ancient
journal, August 2011

Dimerization and DNA recognition rules of mithramycin and its analogues
journal, March 2016

The aldo-keto reductases (AKRs): Overview
journal, June 2015

Studies on the structure of olivomycin a and mithramycin by 1H and 13C nuclear magnetic resonance spectroscopy
journal, January 1981

Mithramycin in the treatment of metastatic ewing's sarcoma
journal, April 1973

Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions
journal, August 2013

Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents
journal, March 1996

Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin
journal, January 1999

How mithramycin stereochemistry dictates its structure and DNA binding function
journal, January 2019

Targeting DnaN for tuberculosis therapy using novel griselimycins
journal, June 2015

Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel
journal, August 2005

An ABC transporter is essential for resistance to the antitumor agent mithramycin in the producerStreptomyces argillaceus
journal, July 1996