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Downstream reactions and engineering in the microbially reconstituted pathway for Taxol

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Abstract

Taxol (a trademarked product of Bristol-Myers Squibb) is a complex isoprenoid natural product which has displayed potent anticancer activity. Originally isolated from the Pacific yew tree (Taxus brevifolia), Taxol has been mass-produced through processes reliant on plant-derived biosynthesis. Recently, there have been alternative efforts to reconstitute the biosynthetic process through technically convenient microbial hosts, which offer unmatched growth kinetics and engineering potential. Such an approach is made challenging by the need to successfully introduce the significantly foreign enzymatic steps responsible for eventual biosynthesis. Doing so, however, offers the potential to engineer more efficient and economical production processes and the opportunity to design and produce tailored analog compounds with enhanced properties. This mini review will specifically focus on heterologous biosynthesis as it applies to Taxol with an emphasis on the challenges associated with introducing and reconstituting the downstream reaction steps needed for final bioactivity.

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Acknowledgments

The authors thank the Milheim Foundation (2006–17) and the National Institutes of Health (GM085323) for support towards projects related to heterologous Taxol biosynthesis.

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  1. Department of Chemical and Biological Engineering, State University of New York at Buffalo, Buffalo, NY, 14260, USA

    Ming Jiang & Blaine A. Pfeifer

  2. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Gregory Stephanopoulos

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  1. Ming Jiang
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Correspondence to Blaine A. Pfeifer.

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Jiang, M., Stephanopoulos, G. & Pfeifer, B.A. Downstream reactions and engineering in the microbially reconstituted pathway for Taxol. Appl Microbiol Biotechnol 94, 841–849 (2012). https://doi.org/10.1007/s00253-012-4016-1

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