Biochemical analysis of the substrate specificity of the β-ketoacyl-acyl carrier protein synthase domain of module 2 of the erythromycin polyketide synthase

Biochemistry

Volumn 43, Issue 51, 2004, Pages 16301-16310

  Wu, Jiaquan ^a   Kinoshita, Kenji ^a   Khosla, Chaitan ^b   Cane, David E ^a  

^a BROWN UNIVERSITY   (United States)

^b Stanford University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACYLATION; BIOCHEMISTRY; BIOSYNTHESIS; PROTEINS; RATE CONSTANTS;

Β-KETOACYL-ACYL CARRIER PROTEIN SYNTHASE (KS); 6-DEOXYERYTHRONOLIDE B SYNTHASE (DEBS); PROTEIN ACYLATION; TRANSTHIOESTERIFICATION;

ENZYME KINETICS;

3 OXOACYL ACYL CARRIER PROTEIN SYNTHASE; CERULENIN; CYSTEAMINE DERIVATIVE; CYSTEINE; POLYKETIDE SYNTHASE; SYNTHETASE; THIOESTER;

ACYLATION; ARTICLE; CHEMICAL ANALYSIS; CONTROLLED STUDY; DISSOCIATION CONSTANT; ENZYME SPECIFICITY; ESCHERICHIA COLI; ESTERIFICATION; NONHUMAN; POLYACRYLAMIDE GEL ELECTROPHORESIS; POLYMERIZATION; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; STOICHIOMETRY;

3-OXOACYL-(ACYL-CARRIER-PROTEIN) SYNTHASE; ACYLATION; CARBON RADIOISOTOPES; KINETICS; POLYKETIDE SYNTHASES; PROTEIN STRUCTURE, TERTIARY; SUBSTRATE SPECIFICITY; TIME FACTORS;

ESCHERICHIA COLI;

EID: 11144303459     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi048147g     Document Type: Article

References (49)

1. Donadio, S., Staver, M. J., Mcalpine, J. B., Swanson, S. J., and Katz, L. (1991) Modular Organization of Genes Required for Complex Polyketide Biosynthesis, Science 252, 675-679.
2. Cortes, J., Haydock, S. F., Roberts, G. A., Bevitt, D. J., and Leadlay, P. F. (1990) An Unusually Large Multifunctional Polypeptide in the Erythromycin-Producing Polyketide Synthase of Saccharopolyspora erythraea, Nature 348, 176-178.
3. Pieper, R., Luo, G. L., Cane, D. E., and Khosla, C. (1995) Cell-free synthesis of polyketides by recombinant erythromycin polyketide synthases, Nature 378, 263-266.
4. Khosla, C., Gokhale, R. S., Jacobsen, J. R., and Cane, D. E. (1999) Tolerance and Specificity of Polyketide Synthases, Annu. Rev. Biochem. 68, 219-253.
5. Cane, D. E., and Walsh, C. T. (1999) The parallel and convergent universes of polyketide synthases and nonribosomal peptide synthetases, Chem. Biol. 6, R319-R325.
6. Walsh, C. T. (2004) Polyketide and nonribosomal peptide antibiotics: Modularity and versatility, Science 303, 1805-1810.
7. Gokhale, R. S., Tsuji, S. Y., Cane, D. E., and Khosla, C. (1999) Dissecting and exploiting intermodular communication in polyketide synthases, Science 284, 482-485.
8. Kinoshita, K., Khosla, C., and Cane, D. E. (2003) Precursor-Directed Biosynthesis: Stereospecificity for Branched-Chain Diketides of the β-Ketoacyl-ACP Synthase Domain 2 of 6-Deoxy-erythronolide B Synthase, Helv. Chim. Acta 86, 3889-3905.
9. Wu, N., Kudo, F., Cane, D. E., and Khosla, C. (2000) Analysis of the Molecular Recognition Features of Individual Modules Derived from the Erythromycin Polyketide Synthase, J. Am. Chem. Soc. 122, 4847-4852.
10. Cane, D. E., Kudo, F., Kinoshita, K., and Khosla, C. (2002) Precursor-directed biosynthesis: Biochemical basis of the remarkable selectivity of the erythromycin polyketide synthase toward unsaturated triketides, Chem. Biol. 9, 131-142.
11. m and V/K in Enzyme Kinetics, J. Chem. Educ. 75, 1153-1157.
12. Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989) Molecular Cloning, A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, Plainview, NY.
13. Jacobsen, J. R., Hutchinson, C. R., Cane, D. E., and Khosla, C. (1997) Precursor-directed biosynthesis of erythromycin analogs by an engineered polyketide synthase, Science 277, 367-369.
14. Harris, R. C., Cutter, A. L., Weissman, K. J., Hanefeld, U., Timoney, M. C., and Staunton, J. (1998) Enantiospecific Synthesis of Analogs of the Diketide Intermediate of the Erythromycin Polyketide Synthase (PKS), J. Chem. Res. 283 (Suppl.), 1230-1247.
15. Kumar, P., Li, Q., Cane, D. E., and Khosla, C. (2003) Intermodular communication in modular polyketide synthases: Structural and mutational analysis of linker mediated protein-protein recognition, J. Am. Chem. Soc. 125, 4097-4102.
16. Bradford, M. (1976) A Rapid and Sensitive Method for the Quantitation of Microgram Quantitites of Protein Utilizing the Principle of Protein-Dye Binding, Anal. Biochem. 72, 248-254.
17. Pfeifer, B. A., Admiraal, S. J., Gramajo, H., Cane, D. E., and Khosla, C. (2001) Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli, Science 291, 1790-1792.
18. Tsukamoto, N., Chuck, J.-A., Luo, G., Kao, C. M., Khosla, C., and Cane, D. E. (1996) 6-Deoxyerythronolide B Synthase 1 Is Specifically Acylated by a Diketide Intermediate at the β-Ketoacyl Acyl Carrier Protein Synthase Domain of Module 2, Biochemistry 35, 15244-15248.
19. Kauppinen, S., Siggaard-Andersen, M., and von Wettstein-Knowles, P. (1988) β-Ketoacyl-ACP Synthase of Escherichia coli: Nucleotide Sequence of the fabB Gene and Identification of the Cerulenin Binding Residue, Carlsberg Res. Commun. 53, 357-370.
20. Watanabe, K., Wang Clay, C. C., Boddy Christopher, N., Cane David, E., and Khosla, C. (2003) Understanding substrate specificity of polyketide synthase modules by generating hybrid multimodular synthases, J. Biol. Chem. 278, 42020-42026.
21. Kitz, R., and Wilson, I. B. (1962) Esters of Methanosulfonic Acid as Irreversible Inhibitors of Acetylcholinesterase, J. Biol. Chem. 237, 3245-3249.
22. Kao, C. M., Luo, G., Katz, L., Cane, D. E., and Khosla, C. (1994) Engineered biosynthesis of a triketide lactone from an incomplete modular polyketide synthase, J. Am. Chem. Soc. 116, 11612-11613.
23. Kao, C. M., Luo, G., Katz, L., Cane, D. E., and Khosla, C. (1995) Manipulation of Macrolide Ring Size by Directed Mutagenesis of a Modular Polyketide Synthase, J. Am. Chem. Soc. 117, 9105-9106.
24. Cortes, J., Wiesmann, K. E. H., Roberts, G. A., Brown, M. J. B., Staunton, J., and Leadlay, P. F. (1995) Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage, Science 268, 1487-1489.
25. Cao, C. M., Luo, G., Katz, L., Cane, D. E., and Khosla, C. (1996) Engineered Biosynthesis of Structurally Diverse Tetraketides by a Trimodular Polyketide Synthase, J. Am. Chem. Soc 118, 9184-9185.
26. Kao, C. M., McPherson, M., McDaniel, R. N., Fu, H., Cane, D. E., and Khosla, C. (1997) Gain of Function Mutagenesis of the Erythromycin Polyketide Synthase. 2. Engineered Biosynthesis of an Eight-Membered Tetraketide Lactone, J. Am. Chem. Soc. 119, 11339-11340.
27. Marsden, A. F. A., Caffrey, P., Aparicio, J. F., Loughran, M. S., Staunton, J., and Leadlay, P. F. (1994) Stereospecific Acyl Transfers on the Erythromycin-Producing Polyketide Synthase, Science 263, 378-380.
28. Lau, J., Fu, H., Cane, D. E., and Khosla, C. (1999) Dissecting the role of acyltransferase domains of modular polyketide synthases in the choice and stereochemical fate of extender units, Biochemistry 38, 1643-1651.
29. Molnar, L, Schupp, T., Ono, M., Zirkle, R. E., Milnamow, M., Nowak-Thompson, B., Engel, N., Toupet, C., Strattmann, A., Cyr, D. D., Gorlach, J., Mayo, J. M., Hu, A., Goff, S., Schmid, J., and Ligon, J. M. (2000) The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90, Chem. Biol. 7, 97-109.
30. Tang, L., Shah, S., Chung, L., Carney, J., Katz, L., Khosla, C., and Julien, B. (2000) Cloning and Heterologous Expression of the Epothilone Gene Cluster, Science 287, 640-642.
31. Cane, D. E., Liang, T. C., Taylor, P. B., Chang, C., and Yang, C. C. (1986) Macrolide biosynthesis. 3. Stereochemistry of the chain-elongation steps of erythromycin biosynthesis, J. Am. Chem. Soc. 108, 4957-4964.
32. Weissman, K. J., Timoney, M. B., Grice, P., Hanefeld, U., Staunton, J., and Leadlay, P. F. (1997) The molecular basis of Celmer's rules: The stereochemistry of the condensation step in chain extension on the erythromycin polyketide synthase, Biochemistry 36, 13849-13855.
33. Holzbaur, I. E., Harris, R. C., Bycroft, M., Cortes, J., Bisang, C., Staunton, J., Rudd, B. A., and Leadlay, P. F. (1999) Molecular basis of Celmer's rules: The role of two ketoreductase domains in the control of chirality by the erythromycin modular polyketide synthase, Chem. Biol. 6, 189-195.
34. Holzbaur, I. E., Ranganathan, A., Thomas, I. P., Kearney, D. J., Reather, J. A., Rudd, B. A., Staunton, J., and Leadlay, P. F. (2001) Molecular basis of Celmer's rules: Role of the ketosynthase domain in epimerisation and demonstration that ketoreductase domains can have altered product specificity with unnatural substrates, Chem. Biol. 8, 329-340.
35. Aparicio, J. F., Molnar, I., Schwecke, T., Konig, A., Haydock, S. F., Khaw, L. E., Staunton, J., and Leadlay, P. F. (1996) Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: Analysis of the enzymatic domains in the modular polyketide synthase, Gene 169, 9-16.
36. Wilkinson, B., Foster, G., Rudd, B. A., Taylor, N. L., Blackaby, A. P., Sidebottom, P. J., Cooper, D. J., Dawson, M. J., Buss, A. D., Gaisser, S., Bohm, I. U., Rowe, C. J., Cortes, J., Leadlay, P. F., and Staunton, J. (2000) Novel octaketide macrolides related to 6-deoxyerythronolide B provide evidence for iterative operation of the erythromycin polyketide synthase, Chem. Biol. 7, 111-117.
37. Beck, B. J., Aldrich, C. C., Fecik, R. A., Reynolds, K. A., and Sherman, D. H. (2003) Iterative chain elongation by a pikromycin monomodular polyketide synthase, J. Am. Chem. Soc. 125, 4682-4683.
38. Wu, N., Tsuji, S. Y., Cane, D. E., and Khosla, C. (2001) Assessing the balance between protein-protein interactions and enzyme-substrate interactions in the channeling of intermediates between polyketide synthase modules, J. Am. Chem. Soc. 123, 6465-6474.
39. Tsuji, S. Y., Cane, D. E., and Khosla, C. (2001) Selective Protein-Protein Interactions Direct Channeling of Intermediates Between Polyketide Synthase Modules, Biochemistry 40, 2326-2331.
40. Broadhurst, R. W., Nietlispach, D., Wheatcroft, M. P., Leadlay, P. F., and Weissman, K. J. (2003) The structure of docking domains in modular polyketide synthases, Chem. Biol. 10, 723-731.
41. Beck, B. J., Aldrich, C. C., Fecik, R. A., Reynolds, K. A., and Sherman, D. H. (2003) Substrate recognition and channeling of monomodules from the pikromycin polyketide synthase, J. Am. Chem. Soc. 125, 12551-12557.
42. Witkowski, A., Joshi, A., Lindqvist, Y., and Smith, S. (1999) Conversion of a β-ketoacyl synthase to a malonyl decarboxylase by replacement of the active-site cysteine with glutamine, Biochemistry 38, 11643-11650.
43. Huang, W., Jia, J., Edwards, P., Dehesh, K., Schneider, G., and Lindqvist, Y. (1998) Crystal structure of β-ketoacyl-acyl carrier protein synthase II from E. coli reveals the molecular architecture of condensing enzymes, EMBO J. 17, 1183-1191.
44. Witkowski, A., Joshi, A. K., and Smith, S. (2002) Mechanism of the β-ketoacyl synthase reaction catalyzed by the animal fatty acid synthase, Biochemistry 41, 10877-10887.
45. Keatinge-Clay, A. T., Maltby, D. A., Medzihradszky, K. F., Khosla, C., and Stroud, R. M. (2004) An antibiotic factory caught in action, Nat. Struct. Mol. Biol. 11, 888-893.
46. Hedstrom, L., Perona, J. J., and Rutter, W. J. (1994) Converting Trypsin to Chymotrypsin: Residue 172 Is a Substrate Specificity Determinant, Biochemistry 33, 8757-8563.
47. Fastrez, J., and Fersht, A. R. (1973) Demonstration of the acyl-enzyme mechanism for the hydrolysis of peptides and anilides by chymotrypsin, Biochemistry 12, 2025-2034.
48. Lau, J., Cane, D. E., and Khosla, C. (2000) Substrate Specificity of the Loading Didomain of the Erythromycin Polyketide Synthase, Biochemistry 39, 10514-10520.
49. Gokhale, R. S., Hunziker, D., Cane, D. E., and Khosla, C. (1999) Mechanism and specificity of the terminal thioesterase domain from the erythromycin polyketide synthase, Chem. Biol. 6, 117-125.