Engineered biosynthesis of structurally diverse tetraketides by a trimodular polyketide synthase

Journal of the American Chemical Society

Volumn 118, Issue 38, 1996, Pages 9184-9185

  Kao, Camilla M ^a   Luo, Guanglin ^b   Katz, Leonard ^c   Cane, David E ^b   Khosla, Chaitan ^a,d  

^a Stanford University ^*  (United States)

^b BROWN UNIVERSITY   (United States)

^c ABBOTT LABORATORIES   (United States)

^d STANFORD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

POLYKETIDE; SYNTHETASE;

ARTICLE; DRUG SYNTHESIS; ENZYME ACTIVITY; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY; THIN LAYER CHROMATOGRAPHY;

EID: 0029804299     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9617552     Document Type: Article

References (25)

1. Donadio, S.; Staver, M. J.; McAlpine, J. B.; Swanson, S. J.: Katz, L. Science 1991, 252, 675-679.
2. Cortes, J.; Haydock, S. F.; Roberts, G. A.; Bevitt, D. J.; Leadlay, P. F. Nature 1990, 348, 176-178.
3. Donadio, S.; Staver, M. J.: McAlpine, J. B.: Swanson, S. J.; Katz, L. Gene 1992, 115, 97-103.
4. Donadio, S.; McAlpine, J. B.; Sheldon, P. J.; Jackson, M.; Katz, L. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 7119-7123.
5. Cane, D. E.; Yang, C.-C. J. Am. Chem. Soc. 1987, 109, 1255-1257.
6. Kao, C. M.; Luo, G.; Katz, L.; Cane, D. E., Khosla, C. J. Am. Chem. Soc. 1994, 116, 11612-11613.
7. Cortes, J.; Wiesmann, K. E. H.; Roberts, G. A.: Brown, M. J. B.; Staunton, J.; Leadlay, P. F. Science 1995, 268, 1487-1489.
8. Brown, M. J. B.; Cortes, J.; Cutter, A. L.; Leadlay, P. F.; Staunton, J. J. Chem. Soc., Chem. Commun. 1995, 1517-1518.
9. Kao, C. M.; Luo, G.; Katz, L.; Cane, D. E.; Khosla, C. J. Am. Chem. Soc. 1995, 117, 9105-9106.
10. III site of pCK7. An Spel site was engineered between L1466 and Q2891 so that the DNA sequence at the fusion is CTGACTAGTCAG.
11. McDaniel, R.; Ebert-Khosla, S.: Hopwood, D., Khosla, C. Science 1993, 262, 1546-1557.
12. Kao, C. M.; Katz, L.; Khosla, C. Science 1994, 265, 509-512.
13. 13C NMR coupling patterns consistent with the derivation of 5 from four intact propionate units.
14. Luo, G.; Pieper, R.; Rosa, A.; Khosla, C.; Cane, D. E. Bioora. Med. Chem. 1996, 4, 995-999. For a discussion on keto-enol equilibria in β-keto esters, see: March, J. Advanced Organic Chemistry, 3rd ed.; J. Wiley: New York, 1985: pp 66-68 and references cited.
15. Luo, G.; Pieper, R.; Rosa, A.; Khosla, C.; Cane, D. E. Bioora. Med. Chem. 1996, 4, 995-999. For a discussion on keto-enol equilibria in β-keto esters, see: March, J. Advanced Organic Chemistry, 3rd ed.; J. Wiley: New York, 1985: pp 66-68 and references cited.
16. A 10% NOE interaction was observed between H-2 and H-5.
17. (a) Evans, D. A.; Nelson, J. V.; Taber, T. R. In Topics in Stereochemistry: Allinger, N. L., Eliel, E. L., Wilen, S. H., Eds.: Wiley: New York, 1982; pp 1-115.
18. (b) Heathcock, C. H. In Asymmetric Synthesis; Morrison, J. D., Ed.: Academic: New York, 1984: Vol. III, pp 111-212.
19. 12 gave 6 labeled at C-3, C-5, and C-7. The presence of only three enriched carbons in 6 is consistent with its formation by decarboxylation of the full-length acyclic tetraketide, followed by hemiketal formation between the C(7)-OH and C-3.
20. + calcd 184.1463, found 184.1464.
21. Evans, D. A.; Bender, S. L.; Morris, J. J. Am. Chem. Soc. 1988, 110, 2506-2526.
22. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155-4156.
23. Patterson, I.; Bower, S.; Tillyer, R. D. Tetrahedron Lett. 1993, 34, 4393-4396.
24. Kinoshita, K.; Takenaka, S.; Hayashi, M. J. Chem. Soc., Chem. Commun. 1988, 943-945.
25. Huber, M. L. B.; Paschal, J. W.; Leeds, J. P.; Kirst, H. A.; Wind, J. A.; Miller, F. D.; Turner, J. R. Antimicrob. Agents Chemother. 1990, 34, 1535-1541.