Production of the antitumor drug epirubicin (4'-epidoxorubicin) and its precursor by a genetically engineered strain of Streptomyces peucetius

Nature Biotechnology
K MadduriC R Hutchinson

Abstract

A fermentation method that bypasses the low-yielding semisynthesis of epirubicin (4'-epidoxorubicin) and 4'-epidaunorubicin, important cancer chemotherapy drugs, has been developed for Streptomyces peucetius. This bacterium normally produces the anthracycline antibiotics, doxorubicin and daunorubicin; the 4'-epimeric anthracyclines are formed by introducing the heterologous Streptomyces avermitilis avrE or Saccharopolyspora eryBIV genes into an S. peucetius dnmV mutant blocked in the biosynthesis of daunosamine, the deoxysugar component of these antibiotics. Product yields were enhanced considerably by replacing the chromosomal copy of dnmV with avrE and by introducing further mutations that can increase daunorubicin and doxorubicin yields in the wild-type strain. This method demonstrates that valuable hybrid antibiotics can be made by combinatorial biosynthesis with bacterial deoxysugar biosynthesis genes.

References

Jul 1, 1975·Journal of Medicinal Chemistry·F ArcamoneC Soranzo
Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·P G Guilfoile, C R Hutchinson
Feb 1, 1987·The Journal of Antibiotics·J J DingerdissenM C Shearer
Jan 11, 1984·Nucleic Acids Research·J DevereuxO Smithies
Nov 3, 1995·Science·R F Service
Jan 1, 1994·Annual Review of Microbiology·H W Liu, J S Thorson
Aug 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·S DonadioL Katz
Jan 1, 1995·Biotechnology·L Katz, S Donadio
Jan 1, 1995·Biotechnology·D J MacNeil
Sep 1, 1996·Trends in Biotechnology·C Khosla, R J Zawada

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Citations

Jun 17, 2008·Applied Microbiology and Biotechnology·Andriy LuzhetskyyAndreas Bechthold
Nov 10, 2012·Applied Biochemistry and Biotechnology·Sohila Zadran, Raphael D Levine
Mar 31, 2004·Bioorganic & Medicinal Chemistry·Eduardo García-JuncedaAlfonso Fernández-Mayoralas
Dec 4, 2003·Journal of Biotechnology·T WeberW Wohlleben
Oct 17, 2001·Trends in Biotechnology·C Méndez, J A Salas
Nov 27, 1998·Trends in Biotechnology·J A Salas, C Méndez
Feb 7, 2001·Current Opinion in Biotechnology·M ChartrainB C Buckland
Apr 3, 2001·Current Opinion in Chemical Biology·J Staunton, B Wilkinson
Nov 18, 1998·Current Opinion in Chemical Biology·D A Johnson, H Liu
Oct 6, 2001·Current Opinion in Microbiology·E Rodriguez, R McDaniel
Mar 6, 1999·Current Opinion in Microbiology·C R Hutchinson
Oct 5, 2010·ACS Chemical Biology·Gavin J WilliamsJon S Thorson
Sep 1, 2005·Journal of the American Chemical Society·Taek Soon LeeYi Tang
Nov 11, 2010·The Journal of Antibiotics·Carlos Olano
Dec 5, 2012·Antimicrobial Agents and Chemotherapy·Christopher D GoodmanHugo Gramajo
Jan 1, 2011·Annual Review of Chemical and Biomolecular Engineering·Lauren B PickensYit-Heng Chooi
Jun 5, 2002·Annual Review of Biochemistry·Xuemei M He, Hung-Wen Liu
Nov 10, 2001·Annual Review of Biomedical Engineering·M KoffasG Stephanopoulos
Oct 11, 2002·Proceedings of the National Academy of Sciences of the United States of America·William A BartonDimitar B Nikolov
Sep 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sachio HeraiMichihiko Kobayashi
Nov 15, 2008·Metabolic Engineering·Lauren B Pickens, Yi Tang
Apr 7, 2007·Trends in Microbiology·José A Salas, Carmen Méndez
Feb 19, 2013·Journal of Basic Microbiology·Ajithkumar VasanthakumarRanjan Prasad
Mar 8, 2011·Microbial Biotechnology·Arnold L Demain, Preeti Vaishnav
Feb 24, 2011·Microbial Biotechnology·Carlos OlanoJosé A Salas
Jan 18, 2006·Journal of Biotechnology·Heinz G Floss
May 2, 2014·Current Opinion in Chemical Biology·Isabelle AndréMagali Remaud-Siméon
Nov 26, 2002·Chemistry & Biology·Wolfgang Wohlleben, Stefan Pelzer
Feb 13, 2001·Metabolic Engineering·W R Strohl
Apr 26, 2016·Medicinal Research Reviews·Enas M Malik, Christa E Müller
May 3, 2000·Molecular Microbiology·S GaisserP F Leadlay
Apr 11, 2000·The Journal of Pharmacy and Pharmacology·R Verpoorte
Apr 27, 2007·Nature·Christopher J ThibodeauxHung-wen Liu

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