Accumulation of the angucycline antibiotic rabelomycin after disruption of an oxygenase gene in the jadomycin B biosynthetic gene cluster of Streptomyces venezuelae.

Microbiology
Ke-Qian YangLeo C Vining

Abstract

DNA from a region downstream of and overlapping the polyketide synthase (PKS) gene cluster for jadomycin B biosynthesis in Streptomyces venezuelae was cloned and sequenced. Analysis of the nucleotide sequence located one complete ORF (ORF6), an incomplete one representing the 3' region of ORF4 in the PKS cluster, and a second incomplete one (ORF7). The deduced amino acid sequences for ORFs 6 and 7 resemble those of oxygenases. Since a plausible biosynthetic pathway for jadomycin B includes an angular polyketide intermediate that undergoes oxidative ring fission before condensation with an amino acid, we subcloned one of the presumptive oxygenase genes (ORF6) in a segregationally unstable shuttle vector (pHJL400) and disrupted it by inserting the gene for apramycin resistance. Transformation of S. venezuelae with the disruption vector and selection for apramycin resistance gave mutants blocked in jadomycin biosynthesis. Southern hybridization confirmed that gene replacement had occurred. Cultures of the mutants accumulated a metabolite identified by comparison with an authentic sample as rabelomycin, a non-nitrogenous polyketide-derived antibiotic originally isolated from Streptomyces olivaceus.

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Apr 1, 1992·Natural Product Reports·J Rohr, R Thiericke
Jan 1, 1990·Annual Review of Genetics·D A Hopwood, D H Sherman
Jun 1, 1990·Journal of Bacteriology·C A OmerD P O'Keefe
Jun 25, 1985·Nucleic Acids Research·P CarterG Winter
Jan 1, 1987·Annual Review of Biochemistry·D W Nebert, F J Gonzalez
Jun 5, 1987·Journal of Molecular Biology·T L PoulosA J Howard
Sep 1, 1970·The Journal of Antibiotics·W C LiuE Meyers
Jan 11, 1984·Nucleic Acids Research·J DevereuxO Smithies
May 1, 1982·The Journal of Antibiotics·N ImamuraS Omura
Dec 3, 1993·Science·R McDanielC Khosla

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Citations

Feb 12, 1998·Protein Science : a Publication of the Protein Society·M H EppinkW J Van Berkel
Jul 27, 2007·Applied Microbiology and Biotechnology·Jian-Ting ZhengKe-Qian Yang
Mar 10, 2007·Journal of the American Chemical Society·Madan K KharelJürgen Rohr
Sep 15, 2005·The Journal of Antibiotics·Jian-Ting ZhengKe-Qian Yang
May 1, 2012·Bioorganic & Medicinal Chemistry Letters·Vinayak S KhodadeHarinath Chakrapani
Mar 19, 2005·Chembiochem : a European Journal of Chemical Biology·Uwe RixJürgen Rohr
May 15, 2013·Chemistry : a European Journal·Xiaoyu Yang, Biao Yu
Apr 1, 2012·European Journal of Organic Chemistry·Ehesan U Sharif, George A O'Doherty
Apr 28, 2010·Chembiochem : a European Journal of Chemical Biology·Yihua ChenKeqian Yang
Feb 17, 2005·Bioorganic & Medicinal Chemistry Letters·David L JakemanShannon C Timmons
Sep 28, 2005·Bioorganic & Medicinal Chemistry Letters·David L JakemanTaryn R Reid
Dec 22, 2011·Natural Product Reports·Madan K KharelJürgen Rohr
Feb 14, 2006·Organic Letters·Ray T SyvitskiDavid L Jakeman
Oct 31, 2015·Microbial Cell Factories·Shanshan LiKeqian Yang
Jun 26, 2003·Journal of the American Chemical Society·Carsten FischerJürgen Rohr
Feb 20, 2002·Chemical Reviews·Steven J. Gould

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