Knowledge-based design of bimodular and trimodular polyketide synthases based on domain and module swaps: A route to simple statin analogues

Chemistry and Biology

Volumn 6, Issue 10, 1999, Pages 731-741

  Ranganathan, Anand ^a   Timoney, Máire ^a   Bycroft, Matthew ^a   Cortés, Jesús ^a,b   Thomas, Iain P ^a   Wilkinson, Barrie ^a,b   Kellenberger, Laurenz ^a,c   Hanefeld, Ulf ^a,d   Galloway, Ian S ^a,e   Staunton, James ^a   Leadlay, Peter F ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

^c F HOFFMANN LA ROCHE LTD   (Switzerland)

^d DELFT UNIVERSITY OF TECHNOLOGY   (Netherlands)

^e Van Den Bergh Foods   (United Kingdom)

Author keywords

Hybrid PKS; Polyketide synthase; Statins; Streptomyces

Indexed keywords

ACYL CARRIER PROTEIN; KETOSYNTHASE; POLYKETIDE SYNTHASE; PROTEIN ENGINEERING; PROTEIN PROTEIN INTERACTION; THIOL ESTER HYDROLASE;

EID: 0033215222     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1074-5521(00)80020-4     Document Type: Article

References (44)

1. 1. Cortés, J., Haydock, S.F., Roberts, G.A., Bevitt, D.J. & Leadlay, P.F. (1990). An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature 348, 176-178.
2. 2. Donadio, S., Staver, M.J., McAlpine, J.B., Swanson, S.J. & Katz, L. (1991). Modular organisation of genes required for complex polyketide biosynthesis. Science 252, 675-679.
3. 3. Bevitt, D.J., Cortés, J., Haydock, S.F. & Leadlay, P.F. (1992). 6-Deoxyerythronolide-B synthase 2 from Saccharopolyspora erythraea. Eur. J. Biochem. 204, 39-49.
4. 4. Swan, D.G., Rodriguez, A.M., Vilches, C., Mendez, C. & Salas, J.A. (1994). Characterisation of a Streptomyces antibioticus gene encoding a type I polyketide synthase which has an unusual coding sequence. Mol. Gen. Genet. 242, 358-362.
5. 5. Schwecke, T., et al., & Leadlay, P.F. (1995). The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. Proc. Natl Acad. Sci. USA 92, 7839-7843.
6. 6. Aparicio, J.F., et al., & Leadlay, P.F. (1996). Organisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygrocopicus: analysis of the enzymatic domains in the modular polyketide synthase. Gene 169, 9-16.
7. 7. MacNeil, D.J., et al., & Danis, S.J. (1992). Complex organisation of the Streptomyces avermitilis genes encoding the avermectin polyketide synthase. Gene 115, 119-125
8. 8. Kuhstoss, S., Huber, M., Turner, J.R., Paschal, J.W. & Rao, R.N. (1997). Production of a novel polyketide through the construction of a hybrid polyketide synthase. Gene 183, 231-236.
9. 9. Caffrey, P., Bevitt, D.J., Staunton, J. & Leadlay, P.F. (1992). Identification of DEBS1, DEBS2 and DEBS3, the multienzyme polypeptides of the erythromycin-producing polyketide synthase from Saccharopolyspora erythraea. FEBS Lett. 304, 225-228.
10. 10. Cortés, J., Wiesmann, K.E.H., Roberts, G.A., Brown, M.J., Staunton, J. & Leadlay, P.F. (1995). Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage. Science 268, 1487-1489.
11. 11. Kao, C.M., Luo, G., Katz, L., Cane, D.E. & Khosla, C. (1995). Manipulation of macrolide ring size by directed mutagenesis of a modular polyketide synthase. J. Am. Chem. Soc. 117, 9105-9106.
12. 12. Wiesmann, K.E.H., Cortés, J., Brown, M.J.B., Cutter, A.L., Staunton, J. & Leadlay, P.F. (1995). Polyketide synthesis in vitro on a modular polyketide synthase. Chem. Biol. 2, 583-589.
13. 13. Pieper, R., Luo, G., Cane, D.E. & Khosla, C. (1995). Cell-free synthesis of polyketides by recombinant erythromycin polyketide synthases. Nature 378, 263-266.
14. 14. Oliynyk, M., Brown, M.J., Cortés, J., Staunton, J. & Leadlay, P.F. (1996). A hybrid modular polyketide synthase obtained by domain swapping. Chem. Biol. 3, 833-839.
15. 15. Ruan, X., et al., & Katz, L. (1997). Acyltransferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives. J. Bacteriol. 179, 6416-6425.
16. 16. McDaniel, R., et al., & Khosla, C. (1997). Gain-of-function mutagenesis of a modular polyketide synthase. J. Am. Chem. Soc. 119, 4309-4310.
17. 17. Aparicio, J.F., Caffrey, P., Marsden, A.F.A., Staunton, J. & Leadlay, P.F. (1994). Limited proteolysis and active site studies of the first multienzyme component of the erythromycin-producing polyketide synthase. J. Biol. Chem. 268, 8524-8528.
18. 18. Staunton, J., Caffrey, P., Aparicio, J.F., Roberts, G.A., Bethell, S.S. & Leadlay, P.F. (1996). Evidence for a double-helical structure for modular polyketide synthases. Nat. Struct. Biol. 3, 188-192.
19. 19. McDaniel, R., Kao, C.M., Hwang, S.J. & Khosla, C. (1997). Engineered intermodular and intramodular polyketide synthase fusions. Chem. Biol. 4, 667-674.
20. 20. Leadlay, P.F. (1997) Combinatorial approaches to polyketide biosynthesis. Curr. Opin. Chem. Biol. 1, 162-168.
21. 21. Khosla, C. (1997). Harnessing the biosynthetic potential of modular polyketide synthases. Chem. Rev. 97, 2577-2590.
22. 22. McDaniel, R., et al., & Ashley, G. (1999). Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel "unnatural" natural products. Proc. Natl Acad. Sci. USA 96, 1846-1851.
23. 23. Alberts, A.W., et al., & Springer, J. (1980) Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc. Natl Acad. Sci. USA 77, 3957-3961.
24. 24. Tobert, J.A., et al., & Bolognese, J.A. (1982) Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoenzymeA reductase, in healthy volunteers. J. Clin. Invest. 69, 913-919.
25. 25. Stokker, GE., et al., & Willard, AK. (1985). 3-Hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors. 1. Structural modification of 5-substituted 3,5-dihydroxypentanoic acids and their lactone derivatives. J. Med. Chem. 28, 347-358.
26. 26. Stokker, GE., et al., & Willard, AK.(1986). 3-Hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors. 3. 7-(3,5-disubstituted [1,1′-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives. J. Med. Chem. 29, 170-181.
27. 27. Böhm, I., Holzbaur, I.E., Hanefeld, U., Cortés, J., Staunton, J. & Leadlay, P.F. (1998). Engineering of a minimal modular polyketide synthase, and targeted alteration of the stereospecificity of polyketide chain extension. Chem. Biol. 5, 407-412.
28. 28. McDaniel, R., Ebert-Khosla, S., Hopwood, D.A. & Khosla, C. (1993). Engineered biosynthesis of novel polyketides. Science 262, 1546-1550.
29. 29. Rowe, C.J., Cortés, J., Gaisser, S., Staunton, J. & Leadlay P.F. (1998). Construction of new vectors for regulated high-level expression in actinomycetes. Gene 216, 215-223.
30. 30. Haydock, S.F., et al., & Leadlay, P.F. (1995). Divergent sequence motifs correlated with the substrate-specificity of (methyl)malonyl-CoA-acyl carrier protein transacylase domains in modular polyketide syntheses. FEBS Lett. 374, 246-248.
31. 31. Marsden, A.F.A., Wilkinson, B., Cortés, J., Dunster, N.J., Staunton, J. & Leadlay, P.F. (1998). Engineering broader specificity into an antibiotic-producing polyketide synthase. Science 279, 199-202.
32. 32. Gokhale, R.S., Tsuji, S.Y., Cane, D.E. & Khosla, C. (1999). Dissecting and exploiting intermodular communication in polyketide synthases. Science 284, 482-485.
33. 33. Zhao, H., Giver, L., Shao, Z., Affholter, J.A. & Arnold, F.H. (1998). Molecular evolution by staggered extension process (StEP) in vitro recombination. Nat. Biotech. 16, 258-261.
34. 34. Stemmer, W.P.C. (1994). Rapid evolution of a protein in vitro by DNA shuffling. Nature 370, 389-391.
35. 35. Kennedy, J., Auclair, K., Kendrew, S.G., Park, C., Vederas, J.C. & Hutchinson, C.R. (1999). Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science 284, 1368-1372.
36. 36. Sambrook, J., Fritsch, E.F. & Maniatis, T. (1989). A Laboratory Manual (2nd edn), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
37. 37. Yamamoto, H., Meurer, K.H. & Hutchinson, C.R. (1986). Transformation of Streptomyces erythraeus. J. Antibiot. 34, 1306-1313.
38. 38. Hopwood, D.A., et al., & Schrempf, H. (1985) Genetic manipulation of Streptomyces: a laboratory manual. John Innes Foundation, Norwich, UK.
39. 39. Dower, W.J., Miller, J.F. & Ragsdale, C.W. (1988). High efficiency transformation of Escherichia coli by high voltage electroporation. Nucleic Acids Res. 16, 6127-6145.
40. 40. Saiki, R.K., et al., & Erlich, H.A. (1988). Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239, 487-491.
41. 41. Chuck, J.A., McPherson, M., Huang, H., Jacobsen, J. R., Khosla, C. & Cane, D. E. (1997). Molecular recognition of diketide substrates by a beta-ketoacyl-acyl carrier protein synthase domain within a bimodular polyketide synthase. Chem. Biol. 4, 757-766.
42. 42. Gabriel, T. & Wessjohann, L. (1997). The chromium-Reformatsky reaction: anti-selective Evans-type aldol reaction with excellent inverse induction at ambient temperature. Tetrahedron Lett. 38, 4387-4388.
43. 43. Evans, D.A., Britton, T.C. & Ellman, J.A. (1987). Contrasteric carboximide hydrolysis with lithium hydroperoxide. Tetrahedron Lett. 28, 6141-6144.
44. 44. Bennett, F., Knight, D.W. & Fenton, G. (1991). Methyl (3R)-3-hydroxy-hex-5-enoate as a precursor to chiral mevinic acid analogues. J. Chem. Soc. Perkin. Trans. I. 133-140.