Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli

Science

Volumn 330, Issue 6000, 2010, Pages 70-74

  Ajikumar, Parayil Kumaran ^a,b   Xiao, Wen Hai ^a   Tyo, Keith E J ^a   Wang, Yong ^c   Simeon, Fritz ^a   Leonard, Effendi ^a   Mucha, Oliver ^a   Phon, Too Heng ^b   Pfeifer, Blaine ^c   Stephanopoulos, Gregory ^a,b  

^a Massachusetts Institute of Technology Cambridge   (United States)

^b SINGAPORE MIT ALLIANCE   (Singapore)

^c Tufts University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACCATIN III; CYTOCHROME P450; ISOPRENOID; PACLITAXEL; PACLITAXEL DERIVATIVE; TAXADIEN 5ALPHA OL; TAXADIENE; UNCLASSIFIED DRUG; 2-C-METHYLERYTHRITOL 4-PHOSPHATE; 3,3-DIMETHYLALLYL PYROPHOSPHATE; ALKENE; DITERPENE; ERYTHRITOL; FARNESYL TRANS TRANSFERASE; HEMITERPENE; HYBRID PROTEIN; INDOLE; INDOLE DERIVATIVE; ISOMERASE; ISOPENTENYL DIPHOSPHATE; ORGANOPHOSPHORUS COMPOUND; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE FERRIHEMOPROTEIN REDUCTASE; SUGAR PHOSPHATE; TAXA-4(20),11(12)-DIENE-5-OL; TAXA-4(5),11(12)-DIENE SYNTHASE; TAXA-4(5),11(12)DIENE; TAXOID; TERPENE;

COLIFORM BACTERIUM; CONIFEROUS TREE; GENETIC ENGINEERING; ISOPRENOID; METABOLISM; MULTIVARIATE ANALYSIS; OPTIMIZATION; OXIDATION; TERPENE;

ARTICLE; BIOSYNTHESIS; CHEMICAL ENGINEERING; CONTROLLED STUDY; DRUG SYNTHESIS; ENZYME METABOLISM; ESCHERICHIA COLI; HUMAN; OXIDATION; PRIORITY JOURNAL; ANALOGS AND DERIVATIVES; BIOREACTOR; ENZYMOLOGY; ESCHERICHIA COLI K 12; FERMENTATION; GENETIC ENGINEERING; GENETICS; METABOLISM; METABOLOMICS; OXIDATION REDUCTION REACTION; TAXUS;

ESCHERICHIA COLI; TAXUS BREVIFOLIA;

ALKENES; BIOREACTORS; CYTOCHROME P-450 ENZYME SYSTEM; DITERPENES; ERYTHRITOL; ESCHERICHIA COLI K12; FARNESYLTRANSTRANSFERASE; FERMENTATION; GENETIC ENGINEERING; HEMITERPENES; INDOLES; ISOMERASES; METABOLIC NETWORKS AND PATHWAYS; METABOLOMICS; NADPH-FERRIHEMOPROTEIN REDUCTASE; ORGANOPHOSPHORUS COMPOUNDS; OXIDATION-REDUCTION; PACLITAXEL; RECOMBINANT FUSION PROTEINS; SUGAR PHOSPHATES; TAXOIDS; TAXUS; TERPENES;

EID: 77957329119     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1191652     Document Type: Article

References (38)

1. D. G. Kingston, Phytochemistry 68, 1844 (2007).
2. M. C. Wani, H. L. Taylor, M. E. Wall, P. Coggon, A. T. McPhail, J. Am. Chem. Soc. 93, 2325 (1971).
3. M. Suffness, M. E. Wall, in Taxol: Science and Applications, M. Suffness, Ed. (CRC, Boca Raton, FL, 1995), pp. 3-26.
4. K. C. Nicolaou et al., Nature 367, 630 (1994).
5. R. A. Holton et al., J. Am. Chem. Soc. 116, 1597 (1994).
6. A. M. Walji, D. W. C. MacMillan, Synlett 18, 1477 (2007).
7. R. A. Holton, R. J. Biediger, P. D. Boatman, in Taxol: Science and Applications, M. Suffness, Ed. (CRC, Boca Raton, FL, 1995), pp. 97-119.
8. D. Frense, Appl. Microbiol. Biotechnol. 73, 1233 (2007).
9. S. C. Roberts, Nat. Chem. Biol. 3, 387 (2007).
10. J. Goodman, V. Walsh, The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug. (Cambridge Univ. Press, Cambridge, 2001).
11. K. E. Tyo, H. S. Alper, G. N. Stephanopoulos, Trends Biotechnol. 25, 132 (2007).
12. P. K. Ajikumar et al., Mol. Pharm. 5, 167 (2008).
13. W. R. Farmer, J. C. Liao, Nat. Biotechnol. 18, 533 (2000).
14. H. Alper, K. Miyaoku, G. Stephanopoulos, Nat. Biotechnol. 23, 612 (2005).
15. M. C. Chang, J. D. Keasling, Nat. Chem. Biol. 2, 674 (2006).
16. V. J. Martin, D. J. Pitera, S. T. Withers, J. D. Newman, J. D. Keasling, Nat. Biotechnol. 21, 796 (2003).
17. D. Morrone et al., Appl. Microbiol. Biotechnol. 85, 1893 (2010).
18. E. Leonard et al., Proc. Natl. Acad. Sci. U.S.A. 107, 13654 (2010).
19. Q. Huang, C. A. Roessner, R. Croteau, A. I. Scott, Bioorg. Med. Chem. 9, 2237 (2001).
20. B. Engels, P. Dahm, S. Jennewein, Metab. Eng. 10, 201 (2008).
21. L. Z. Yuan, P. E. Rouvière, R. A. Larossa, W. Suh, Metab. Eng. 8, 79 (2006).
22. Y. S. Jin, G. Stephanopoulos, Metab. Eng. 9, 337 (2007).
23. H. H. Wang et al., Nature 460, 894 (2009).
24. D. Klein-Marcuschamer, P. K. Ajikumar, G. Stephanopoulos, Trends Biotechnol. 25, 417 (2007).
25. J. M. Dejong et al., Biotechnol. Bioeng. 93, 212 (2006).
26. Materials and methods are available as supporting material on Science Online.
27. K. L. Jones, S. W. Kim, J. D. Keasling, Metab. Eng. 2, 328 (2000).
28. R. Kaspera, R. Croteau, Phytochem. Rev. 5, 433 (2006).
29. S. Jennewein, R. M. Long, R. M. Williams, R. Croteau, Chem. Biol. 11, 379 (2004).
30. M. A. Schuler, D. Werck-Reichhart, Annu. Rev. Plant Biol. 54, 629 (2003).
31. E. Leonard, M. A. Koffas, Appl. Environ. Microbiol. 73, 7246 (2007).
32. D. R. Nelson, Arch. Biochem. Biophys. 369, 1 (1999).
33. S. Jennewein et al., Biotechnol. Bioeng. 89, 588 (2005).
34. D. Rontein et al., J. Biol. Chem. 283, 6067 (2008).
35. W. R. Farmer, J. C. Liao, Biotechnol. Prog. 17, 57 (2001).
36. S. Jennewein, M. R. Wildung, M. Chau, K. Walker, R. Croteau, Proc. Natl. Acad. Sci. U.S.A. 101, 9149 (2004).
37. K. Walker, R. Croteau, Phytochemistry 58, 1 (2001).
38. We thank R. Renu for extraction, purification, and characterization of metabolite Indole; C. Santos for providing the pACYCmelA plasmid, constructive suggestions during the experiments, and preparation of the manuscript; D. Dugar, H. Zhou, and X. Huang for helping with experiments and suggestions; and K. Hiller for data analysis and comments on the manuscript. We gratefully acknowledge support by the Singapore-MIT Alliance (SMA-2) and NIH, grant 1-R01-GM085323-01A1. B.P. acknowledges the Milheim Foundation Grant for Cancer Research 2006-17. A patent application that is based on the results presented here has been filed by MIT. P.K.A. designed the experiments and performed the engineering and screening of the strains; W-H.X. performed screening of the strains, bioreactor experiments, and GC-MS analysis; F.S. carried out the quantitative PCR measurements; O.M. performed the extraction and characterization of taxadiene standard; E.L., Y.W., and B.P. supported with cloning experiments; P.K.A., K.E.J.T., T.H.P., B.P. and G.S. analyzed the data; P.K.A., K.E.J.T., and G.S. wrote the manuscript; G.S. supervised the research; and all of the authors contributed to discussion of the research and edited and commented on the manuscript.