Journal of Microbiology and Biotechnology

  • 제13권4호
  • /
  • Pages.613-619
  • /
  • 2003
  • /
  • 1017-7825(pISSN)
  • /
  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
권호 표지

Premature Release of Polyketide Intermediates by Hybrid Polyketide Synthase in Amycolatopsis mediterranei S699

  • Hong, Jay-Sung-Joong (Interdisciplinary Program of Biochemical Engineering and Biotechnology, Seoul National University) ;
  • Choi, Cha-Yong (Interdisciplinary Program of Biochemical Engineering and Biotechnology, Seoul National University, School of Chemical Engineering, College of Engineering, Seoul National University) ;
  • Yoo, Yeo-Joon (School of Chemical Engineering and Bioengineering, University of Ulsan)
  • 발행 : 2003.08.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The polyketide backbone of rifamycin B is assembled by the type I rifamycin polyketide synthase (PKS) encoded by the rifA-rifE genes. In order to produce novel analogs of rifamycin via engineering of the PKS genes, inactivation of the ${\beta}-ketoacyl:acyl$ carrier protein reductase (KR) domain in module 8 of rifD, by site-specific mutagenesis of the NADPH binding site, was attempted. Module 8 contains a nonfunctional dehydratase (DH) domain and a functional KR domain that is involved in the reduction of the ${\beta}-carbonyl$ group, resulting in the C-21 hydroxyl of rifamycin B. This mutant strain produced linear polyketides, from tetraketide to octaketide, which were also produced by a rifD-disruption mutant as a consequence of premature termination of the polyketide assembly. Another attempt to replace the DH domain of module 7, which has been considered nonfunctional, with a functional homolog derived from module 7 of rapamycin-producing PKS also resulted in the production of linear polyketides, including the heptaketide intermediate and its precursors. Premature release of the carbon chain assembly intermediates is an unusual property of the rifamycin PKS. that is not seen in other PKSs such as the erythromycin PKS.

키워드

참고문헌

  1. Chem. Biol. v.5 Biosynthesis of the ansamycin antibiotic rifamycin:Deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis Mediterranei S699 August,P.R.;L.Tang;Y.J.Yoon;S.Ning;R.Muller;T.W.Yu;M.Taylor;D.Hoffmann;C.G.Kim;X.Zhang;C.R.Hutchinson;H.G.Floss https://doi.org/10.1016/S1074-5521(98)90141-7
  2. Sov. J. Bioorg. Chem. v.9 RNA polymerase-rifamycin. A molecular model of inhibition Chertov,O.Y.;A.N.Obukhov;V.M.Lipkin
  3. J. Microbiol. Biotechnol. v.12 no.2 Identification of Streptomyces sp. producing new polyene antibiotics and in vivo antimicrobial activity of Tetrin C against phytopathogenic fungi Choi,W.C.;S.Y.Hwang;T.K.Park;S.K.Kim
  4. Tubercule v.68 In vitro activity of new rifamycins against rifampicin-resistant M. tuberculosis and MAIS complex mycobacteria Dickinson,J.M.;D.A.Mitchison https://doi.org/10.1016/0041-3879(87)90053-5
  5. J. Antibiotics v.53 no.5 Thioesterase and the premature termination of polyketide chain elongation in rifamycin B biosynthesis by Amycolatopsis mediterranei S699 Doi-Katayama, Y.;Y.J.Yoon;C.Y.Choi;T.W.Yu;H.G.Floss;C.R.Hutchinson https://doi.org/10.7164/antibiotics.53.484
  6. J. Antibiotics v.34 A genetic approach to the biosynthesis of the rifamycin chromophore in Nocardia mediterranei. Ⅲ. Isolation and idenification of 3-amino-5-hydroxybenzoic acid as a direct precursor of the seven carbon amino starter-unit Ghisalba,O.;J.Nuesch https://doi.org/10.7164/antibiotics.34.64
  7. Curr. Opin. Microbiol. v.1 Combinatorial biosynthesis for new drug discovery Hutchinson,C.R.
  8. Chem. Rev. v.97 Manipulation of modular polyketide synthases Katz,L. https://doi.org/10.1021/cr960025+
  9. Chem. Rev. v.97 Harnessing the biosynthetic potential of mocular polyketide synthase Khosla,C. https://doi.org/10.1021/cr960027u
  10. Practical Streptomyces Genetics Kieser,T.;M.J.Bibb;M.J.Buttner;K.F.Chater;D.A.Hopwood
  11. Biotechnology of Antibiotics Polyketide antibiotics produced by type-I multifunctional enzymes:rifamycins Lancini,G.;B.Cavalleri;W.R.Strohl(ed.)
  12. Proc. Natl. Acad. Sci. USA v.96 Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel unnatural natural products McDaniel,R.;A.Thamchaipenet;C.Gustafsson;H.Fu;M.Betlach;G.Ashley https://doi.org/10.1073/pnas.96.5.1846
  13. Science v.257 The crisis in antibiotic research New,H.C. https://doi.org/10.1126/science.257.5073.1064
  14. Helv. Chim. Acta v.56 On the constitution and configuration of rifamycins B, O, S and SV. Oppolzer,W.;V.Prelog https://doi.org/10.1002/hlca.19730560717
  15. Fortschr. Chem. Org. Naturst. v.33 Chemistry of the ansamycin antibiotics Rinehart, Jr.K.L.;L.S.Shields https://doi.org/10.1007/978-3-7091-3262-3_3
  16. Science v.14 Rifamycin, a new antibiotic:Preliminary report. Farmaco. Ed. Sensi,P.;P.Margalith;M.T.Timbal
  17. J. Microbiol. Biotechnol. v.11 no.4 A new analog of antimycin from streptomyces sp. MO3033 Seo,Y.W.;K.W.Cho;J.R.Rho;S.J.Mo;J.H.Shin
  18. Clin. Microbiol. Rev. v.8 Tuberculosis in the AIDS era. Sepkowitz,K.A.;J.Rafalli;L.Riley;T.E.Kiehn;D.Armstrong
  19. Microbiology v.145 Intermediates of rifamycin polyketide synthase produced by an Amycolatopsis mediterranei mutant with inactivated rifF gene Stratmann,A.;C.Toupet;W.Schilling;R.Traber;L.Oberer;T.Schupp
  20. Chem. Biol. v.7 Formation of functional heterologous complexes using subunits from the picromycin, erythromycin and oleandomycin polyketide synthase Tang,L.;H.Fu;R.McDaniel https://doi.org/10.1016/S1074-5521(00)00073-9
  21. Gene v.216 Characterization of the enzymatic domains on the modular polyketide synthase involved in rifamycin B biosynthesis by Amycolatopsis metiterrenei Tang,L.;Y.J.Yoon;C.Y.Choi;C.R.Hutchinson
  22. Science v.264 Reviving the antibiotic miracle Travis,J.
  23. Science v.252 An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea Weber,J.M.;J.O.Leung;S.J.Swanson;K.B.Idler;J.B.McAlpine https://doi.org/10.1126/science.2011746
  24. Am. Rev. Respir. Dis v.126 In vitro susceptibility of Mycobacterium avium complex and Mycobacterium tuberculosis strains to a spiropiperidyl rifamycin Woodley,C.L.;J.O.Kilburn
  25. Chem. Biol. v.9 no.2 Generation of multiple bioactive macrolides by hybrid modular polyketide synthases in Streptomyces venezuelae Yoon,Y.J.;B.J.Beck;B.S.Kim;H.Y.Kang;K.A.Reynolds;D.H.Sherman https://doi.org/10.1016/S1074-5521(02)00095-9
  26. Proc. Natl. Acad. Sci. USA v.96 Direct evidence that the rifamycin polyketide synthase assembles polyketide chains processively Yu,T.W.;Y.Shen;Y.Doi-Katayama;L.Tang;C.Park;B.S.Moore;C.R.Hutchinson;H.G.Floss https://doi.org/10.1073/pnas.96.16.9051