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  • Perspective
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Production of isoprenoid pharmaceuticals by engineered microbes

Nature Chemical Biology volume 2, pages 674–681 (2006)Cite this article

Abstract

Throughout human history, natural products have been the foundation for the discovery and development of therapeutics used to treat diseases ranging from cardiovascular disease to cancer. Their chemical diversity and complexity have provided structural scaffolds for small-molecule drugs and have consistently served as inspiration for medicinal design. However, the chemical complexity of natural products also presents one of the main roadblocks for production of these pharmaceuticals on an industrial scale. Chemical synthesis of natural products is often difficult and expensive, and isolation from their natural sources is also typically low yielding. Synthetic biology and metabolic engineering offer an alternative approach that is becoming more accessible as the tools for engineering microbes are further developed. By reconstructing heterologous metabolic pathways in genetically tractable host organisms, complex natural products can be produced from inexpensive sugar starting materials through large-scale fermentation processes. In this Perspective, we discuss ongoing research aimed toward the production of terpenoid natural products in genetically engineered Escherichia coli and Saccharomyces cerevisiae.

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Figure 1: Transplantation of a biosynthetic pathway from the natural host into a microbial host.
Figure 2: The search for a P450 for the oxidation of amorphadiene.

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Acknowledgements

We would like to thank D. Pitera, E. Paradise and D.-K. Ro for helpful discussions. M.C.Y.C acknowledges a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund. Isoprenoid research in the Keasling laboratory has been funded by the University of California Discovery Grant Program, the US National Science Foundation, Maxygen, Diversa and the Bill & Melinda Gates Foundation.

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  1. California Institute for Quantitative Biomedical Research, University of California Berkeley, Berkeley, 94720-3224, California, USA

    Michelle C Y Chang & Jay D Keasling

  2. Department of Chemical Engineering, Department of Bioengineering, University of California Berkeley, Berkeley, 94720, California, USA

    Michelle C Y Chang & Jay D Keasling

  3. Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA

    Michelle C Y Chang & Jay D Keasling

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Correspondence to Jay D Keasling.

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Jay Keasling is a founder of Amyris Biotechnologies, a company that may eventually use the gene and engineered yeast described in the publication Nature 440, 940-943 (2006) to produce artemisinin. However, neither Amyris Biotechnologies nor the University of California will make any profit from the production and sale of artemisinin, the anti-malarial drug.

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Chang, M., Keasling, J. Production of isoprenoid pharmaceuticals by engineered microbes. Nat Chem Biol 2, 674–681 (2006). https://doi.org/10.1038/nchembio836

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