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Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli
Open accessAbstract
Toward Microbial Taxol: Taxol, a minor chemical constituent of yew tree bark, has provided a potent cancer treatment. Production methods presently rely on plant cell cultures. Ajikumar et al. (p. 70 ; see the Perspective by Liu and Khosla ) engineered Escherichia coli cells to produce a key taxol precursor, in which the polycyclic carbon skeleton is intact. The approach relied on optimizing the relative activity of two pathways, the first of which synthesized isoprenoid building blocks that were then stitched together with the second pathway. Accumulation of indole as a by-product inhibited the isoprenoid pathway—an insight that should facilitate more efficient engineered biosynthesis of a wide range of commercially important isoprenoid derivatives.
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Cites
Programming cells by multiplex genome engineering and accelerated evolution
Wang, H. H., Isaacs, F. J., Carr, P. A., Sun, Z. Z., Xu, G., Forest, C. R., & Church, G. M. (2009) · Nature · doi:10.1038/nature08187 · Cited by 1,529
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Nielsen, J., & Keasling, J. D. (2016) · Cell · doi:10.1016/j.cell.2016.02.004 · Cited by 1,378
Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds
Zalatan, J. G., Lee, M. E., Almeida, R., Gilbert, L. A., Whitehead, E. H., La Russa, M., Tsai, J. C., Weissman, J. S., Dueber, J. E., Qi, L. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.052 · Cited by 938
A Highly Characterized Yeast Toolkit for Modular, Multipart Assembly
Lee, M. E., DeLoache, W. C., Cervantes, B., & Dueber, J. E. (2015) · ACS Synthetic Biology · doi:10.1021/sb500366v · Cited by 916
An engineered microbial platform for direct biofuel production from brown macroalgae
Wargacki, A. J., Leonard, E., Win, M. N., Regitsky, D. D., Santos, C. N. S., Kim, P. B., Cooper, S. R., Raisner, R. M., Herman, A., Sivitz, A. B., et al. (2012) · Science · doi:10.1126/science.1214547 · Cited by 734
Self-citationZhou, K., Qiao, K., Edgar, S., & Stephanopoulos, G. (2015) · Nature Biotechnology · doi:10.1038/nbt.3095 · Cited by 710
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Metadata
- Authors
- Ajikumar, P. K., Xiao, W.-H., Tyo, K. E. J., Wang, Y., Simeon, F., Leonard, E., Mucha, O., Phon, T. H., Pfeifer, B., & Stephanopoulos, G.
- Venue
- Science
- Published
- 2010-10
- Volume
- 330
- Issue
- 6000
- Pages
- 70-74
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1579030151
- Cited by
- 1,677
- References
- 1
- FWCI
- 31.78
- Type
- journal article
- Language
- en
- Open access
- green
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- Ajikumar, P. K., Xiao, W.-H., Tyo, K. E. J., Wang, Y., Simeon, F., Leonard, E., Mucha, O., Phon, T. H., Pfeifer, B., & Stephanopoulos, G. (2010). Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli. Science. https://doi.org/10.1126/science.1191652
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