Use of an inducible promoter for antibiotic production in a heterologous host.

Applied Microbiology and Biotechnology
Volker DangelBertolt Gust

Abstract

The biosynthetic gene cluster of the aminocoumarin antibiotic novobiocin comprises 20 coding sequences. Sixteen of them code for essential enzymes for novobiocin formation, transcribed in the form of a single 18-kb polycistronic mRNA. In the present study, we replaced the genuine promoter of this operon by the tetracycline-inducible promoter tcp830 and at the same time deleting the two pathway-specific positive regulator genes of novobiocin biosynthesis. The heterologous producer Streptomyces coelicolor M512 harboring the modified gene cluster produced, upon addition of 2 mg L(-1) of the inducer compound anhydrotetracyline, 3.4-fold more novobiocin than strains carrying the unmodified cluster. A second tcp830 promoter was inserted in the middle of the 18-kb operon in order to ensure adequate transcription of the rearmost genes. However, this did not lead to a further increase of novobiocin formation, showing that a single tcp830 promoter was sufficient to achieve high transcription of all 16 genes of the operon. A high induction of novobiocin formation was achieved within a wide range of anhydrotetracyline concentrations (0.25-2.0 mg L(-1)). Growth of the strains was not affected by these concentrations. The inducer compound co...Continue Reading

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Citations

Mar 22, 2013·Applied Microbiology and Biotechnology·Deyao DuHuarong Tan
Apr 16, 2013·Applied Microbiology and Biotechnology·Maksym Myronovskyi, Andriy Luzhetskyy
Mar 9, 2013·Microbiology and Molecular Biology Reviews : MMBR·Gang LiuHuarong Tan
Jan 19, 2012·Microbial Cell Factories·Sujata Vijay SohoniAnna Eliasson Lantz
Oct 16, 2013·Journal of Industrial Microbiology & Biotechnology·Yuriy RebetsAndriy Luzhetskyy
Sep 14, 2015·Journal of Industrial Microbiology & Biotechnology·Richard H Baltz
Feb 11, 2016·Applied Microbiology and Biotechnology·Jianwei ChenHong Wang
Jan 23, 2016·Applied Microbiology and Biotechnology·Paulina BekieschAlexander Kristian Apel
Apr 2, 2013·Current Opinion in Biotechnology·Hans-Jörg FraschRainer Breitling
Apr 25, 2017·Biotechnology and Bioengineering·Joachim KoepffMarco Oldiges
Jul 21, 2016·Natural Product Reports·Maksym Myronovskyi, Andriy Luzhetskyy
Oct 27, 2017·FEMS Microbiology Letters·Jiafang FuGuangxiang Cao
Nov 10, 2010·Natural Product Reports·Haoran ZhangBlaine A Pfeifer
Jun 4, 2016·Archiv der Pharmazie·Paulina BekieschAlexander K Apel
Aug 28, 2019·Natural Product Reports·Maksym Myronovskyi, Andriy Luzhetskyy
Jun 12, 2017·Applied Microbiology and Biotechnology·Chengjun ZhuShouwen Chen
Jan 23, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nils BöhringerTill F Schäberle

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