Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis

Science

Volumn 284, Issue 5418, 1999, Pages 1368-1372

  Kennedy, Jonathan ^a   Auclair, Karine ^b   Kendrew, Steven G ^a,c   Park, Cheonseok ^a   Vederas, John C ^b   Hutchinson, C Richard ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b UNIVERSITY OF ALBERTA   (Canada)

^c SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

MEVINOLIN; POLYKETIDE; SYNTHETASE;

ARTICLE; BIOSYNTHESIS; CARBOXY TERMINAL SEQUENCE; DNA SEQUENCE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME STRUCTURE; ENZYME SUBSTRATE; GENE CLUSTER; GENE MUTATION; NONHUMAN; PRIORITY JOURNAL; SEQUENCE ANALYSIS;

ASPERGILLUS; ASPERGILLUS NIDULANS; BINDING SITES; BUTYRATES; ESTERASES; FUNGAL PROTEINS; GENES, FUNGAL; LOVASTATIN; MULTIENZYME COMPLEXES; NAPHTHALENES;

EID: 0033591447     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.284.5418.1368     Document Type: Article

References (40)

1. J. G. Hardman et al., Eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics (McGraw-Hill, New York, 1996), pp. 885-887.
2. R. N. Moore et al., J. Am. Chem. Soc. 107, 3694 (1985); K. Wagschal, Y. Yoshizawa, D. J. Witter, Y. Liu, J. C. Vederas, J. Chem. Soc. Perkin Trans. 1, 2357 (1996).
3. R. N. Moore et al., J. Am. Chem. Soc. 107, 3694 (1985); K. Wagschal, Y. Yoshizawa, D. J. Witter, Y. Liu, J. C. Vederas, J. Chem. Soc. Perkin Trans. 1, 2357 (1996).
4. R. L. Monaghan and J. S. Tkacz, Annu. Rev. Microbiol. 44, 271 (1990); D. O'Hagan, The Polyketide Metabolites (Ellis Norwood, New York, 1991).
5. R. L. Monaghan and J. S. Tkacz, Annu. Rev. Microbiol. 44, 271 (1990); D. O'Hagan, The Polyketide Metabolites (Ellis Norwood, New York, 1991).
6. L. Katz, Chem. Rev. 97, 2557 (1997); J. Staunton and B. Wilkinson, ibid., p. 2611; D. E. Cane, C. T. Walsh, C. Khosla, Science 282, 63 (1998).
7. L. Katz, Chem. Rev. 97, 2557 (1997); J. Staunton and B. Wilkinson, ibid., p. 2611; D. E. Cane, C. T. Walsh, C. Khosla, Science 282, 63 (1998).
8. L. Katz, Chem. Rev. 97, 2557 (1997); J. Staunton and B. Wilkinson, ibid., p. 2611; D. E. Cane, C. T. Walsh, C. Khosla, Science 282, 63 (1998).
9. S. Donadio et al., Science 252, 675 (1991).
10. C. R. Hutchinson, Chem. Rev. 97, 2525 (1997); D. A. Hopwood, ibid., p. 2465.
11. C. R. Hutchinson, Chem. Rev. 97, 2525 (1997); D. A. Hopwood, ibid., p. 2465.
12. S. Smith. FASEB J. 8, 1248 (1994).
13. Y. Yamamoto, A. Hori, C. R. Hutchinson, J. Am. Chem. Soc. 107, 2471 (1985).
14. C. Yang, M. S. Rose, B. G. Turgeon, O. C. Yoder, Plant Cell 8, 139 (1996); Y. Kono and J. M. Daly, Bioorg. Chem. 8, 397 (1979).
15. C. Yang, M. S. Rose, B. G. Turgeon, O. C. Yoder, Plant Cell 8, 139 (1996); Y. Kono and J. M. Daly, Bioorg. Chem. 8, 397 (1979).
16. D. J. Witter and J. C. Vederas, J. Org. Chem. 61, 2613 (1996).
17. L. R. Treiber, R. A. Reamer, C. S. Rooney, H. G. Ramjit, J. Antibiot. 42, 30 (1989); T. Nakamura, D. Komagata, S. Murakawa, K. Sakai, A. Endo, ibid. 43, 1597 (1990).
18. L. R. Treiber, R. A. Reamer, C. S. Rooney, H. G. Ramjit, J. Antibiot. 42, 30 (1989); T. Nakamura, D. Komagata, S. Murakawa, K. Sakai, A. Endo, ibid. 43, 1597 (1990).
19. Y. Liu, Z. Li, J. C. Vederas, Tetrahedron 54, 15937 (1998).
20. J. K. Chan, R. N. Moore, T. T. Nakashima, J. C. Vederas, J. Am. Chem. Soc. 105, 3334 (1983); Y. Yoshizawa, D. J. Witter, Y. Liu, J. C. Vederas, ibid. 116, 2693 (1994).
21. J. K. Chan, R. N. Moore, T. T. Nakashima, J. C. Vederas, J. Am. Chem. Soc. 105, 3334 (1983); Y. Yoshizawa, D. J. Witter, Y. Liu, J. C. Vederas, ibid. 116, 2693 (1994).
22. V. A. Vinci et al., U.S. Patent 5,744,350 (28 April 1998); L. Hendrickson et al., in preparation.
23. V. A. Vinci et al., U.S. Patent 5,744,350 (28 April 1998); L. Hendrickson et al., in preparation.
24. For the DNA sequence and selected sequence analysis data plus experimental details, see Science Online (www.sciencemag.org/feature/data/990861.shl).
25. D. Konz and M. A. Marahiel, Chem. Biol. 6, R39 (1999).
26. P. E. Kolattukudy, N. D. Fernandes, A. K. Azad, A. M. Fitzmaurice, T. D. Sirakova, Mol. Microbiol. 24, 263 (1997); S. T. Cole et al., Nature 393, 537 (1998); D. L. Rainwater and P. E. Kolattukudy, J. Biol. Chem. 260, 616 (1985); A. M. Fitzmaurice and P. E. Kolattukudy, ibid. 273, 8033 (1998).
27. P. E. Kolattukudy, N. D. Fernandes, A. K. Azad, A. M. Fitzmaurice, T. D. Sirakova, Mol. Microbiol. 24, 263 (1997); S. T. Cole et al., Nature 393, 537 (1998); D. L. Rainwater and P. E. Kolattukudy, J. Biol. Chem. 260, 616 (1985); A. M. Fitzmaurice and P. E. Kolattukudy, ibid. 273, 8033 (1998).
28. P. E. Kolattukudy, N. D. Fernandes, A. K. Azad, A. M. Fitzmaurice, T. D. Sirakova, Mol. Microbiol. 24, 263 (1997); S. T. Cole et al., Nature 393, 537 (1998); D. L. Rainwater and P. E. Kolattukudy, J. Biol. Chem. 260, 616 (1985); A. M. Fitzmaurice and P. E. Kolattukudy, ibid. 273, 8033 (1998).
29. P. E. Kolattukudy, N. D. Fernandes, A. K. Azad, A. M. Fitzmaurice, T. D. Sirakova, Mol. Microbiol. 24, 263 (1997); S. T. Cole et al., Nature 393, 537 (1998); D. L. Rainwater and P. E. Kolattukudy, J. Biol. Chem. 260, 616 (1985); A. M. Fitzmaurice and P. E. Kolattukudy, ibid. 273, 8033 (1998).
30. For experimental details of the isolation and structural elucidation of 7 and 8 and dihydromonacolin L as well as its cell-free synthesis, see K. Auclair, S. G. Kendrew, J. Kennedy, C. R. Hutchinson, J. C. Vederas, in preparation. For NMR and MS spectral characteristics of these three compounds, see Science Online (www.sciencemag.org/feature/data/990861.shl).
31. For experimental details of the isolation and structural elucidation of 7 and 8 and dihydromonacolin L as well as its cell-free synthesis, see K. Auclair, S. G. Kendrew, J. Kennedy, C. R. Hutchinson, J. C. Vederas, in preparation. For NMR and MS spectral characteristics of these three compounds, see Science Online (www.sciencemag.org/feature/data/990861.shl).
32. J.-H. Ahn and J. D. Walton, Mol. Gen. Genet 260, 462 (1998).
33. The functional interaction of LNKS and LovC has a precedent in an NRPS, syringomycin synthetase, where an adenylation domain encoded by a separate gene interacts with a condensation domain in the multifunctional SyrE protein [E. Guenzi, G. Galli, I. Grgurina, D. C. Cross, G. Grandi, J. Biol. Chem. 273, 32857 (1998)] and in the biosynthesis of coronatine, where monofunctional and multifunctional PKSs interact [V. Rangaswamy et al., Proc. Natl. Acad. Sci. U.S.A. 95, 15469 (1998)].
34. The functional interaction of LNKS and LovC has a precedent in an NRPS, syringomycin synthetase, where an adenylation domain encoded by a separate gene interacts with a condensation domain in the multifunctional SyrE protein [E. Guenzi, G. Galli, I. Grgurina, D. C. Cross, G. Grandi, J. Biol. Chem. 273, 32857 (1998)] and in the biosynthesis of coronatine, where monofunctional and multifunctional PKSs interact [V. Rangaswamy et al., Proc. Natl. Acad. Sci. U.S.A. 95, 15469 (1998)].
35. K. Katayama, T. Kobayashi, H. Oikawa, M. Honma, A. Ichihara, Biochim. Biophys. Acta 1384, 387 (1998); A. Ichihara and H. Oikawa, Curr. Org. Chem. 2, 365 (1998); H. Oikawa, Y. Suzuki, A. Naya, K. Katayama, A. Ichihara, J. Am. Chem. Soc. 116, 3605 (1994).
36. K. Katayama, T. Kobayashi, H. Oikawa, M. Honma, A. Ichihara, Biochim. Biophys. Acta 1384, 387 (1998); A. Ichihara and H. Oikawa, Curr. Org. Chem. 2, 365 (1998); H. Oikawa, Y. Suzuki, A. Naya, K. Katayama, A. Ichihara, J. Am. Chem. Soc. 116, 3605 (1994).
37. K. Katayama, T. Kobayashi, H. Oikawa, M. Honma, A. Ichihara, Biochim. Biophys. Acta 1384, 387 (1998); A. Ichihara and H. Oikawa, Curr. Org. Chem. 2, 365 (1998); H. Oikawa, Y. Suzuki, A. Naya, K. Katayama, A. Ichihara, J. Am. Chem. Soc. 116, 3605 (1994).
38. For detailed analysis of the function of ORFs 1, 2, 8,10, 12-18, lovA, and lovE, see J. Kennedy, C. Park, K. Auclair, J. C. Vederas, C. R. Hutchinson, in preparation.
39. M. Jacobs and U. Stahl, in The Mycota II. Genetics and Biotechnology, U. Kuck, Ed. (Springer-Verlag, Berlin, 1995), p. 155.
40. We thank C. Reeves and P. McAda (MDS Panlabs Inc.) for the lovB gene and LNKS antiserum, and unpublished information to appear in (14); A. Endo and Merck and Co. for chemical standards; and K. Watts for assistance with DNA sequencing. Supported by NIH grant AI43031, the University of Wisconsin Graduate School, the Natural Sciences and Engineering Research Council of Canada, and the Alberta Heritage Foundation for Medical Research.