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  • Perspective
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Opportunities in metabolic engineering to facilitate scalable alkaloid production

Nature Chemical Biology volume 5, pages 292–300 (2009)Cite this article

Abstract

Numerous drugs and drug precursors in the current pharmacopoeia originate from plant sources. The limited yield of some bioactive compounds in plant tissues, however, presents a significant challenge for large-scale drug development. Metabolic engineering has facilitated the development of plant cell and tissue systems as alternative production platforms that can be scaled up in a controlled environment. Nevertheless, effective metabolic engineering approaches and the predictability of genetic transformations are often obscured due to the myriad cellular complexities. Progress in systems biology has aided the understanding of genome-wide interconnectivities in plant-based systems. In parallel, the bottom-up assembly of plant biosynthetic pathways in microorganisms demonstrated the possibilities of a new means of production. In this Perspective, we discuss the opportunities and challenges of implementing metabolic engineering in various platforms for the synthesis of natural and unnatural plant alkaloids.

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Figure 1: Relative complexities of plant and microbial systems.

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Acknowledgements

The authors are grateful for the constructive discussion and contribution of M. Tackett (Whitehead Institute for Biomedical Research and Department of Biology, MIT). Research in the Prather laboratory is supported by the US National Science Foundation/Synthetic Biology Engineering Research Center (SynBERC; grant no. 0540879) and the MIT Energy Initiative (grant no. 6917278). Research in the O'Connor laboratory is funded by the US National Institutes of Health (GM074820) and the US National Science Foundation (MCB-0719120).

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  1. Effendi Leonard and Kristala Jones Prather are in the Department of Chemical Engineering, and Weerawat Runguphan and Sarah O'Connor are in the Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. Effendi Leonard and Weerawat Runguphan contributed equally to this work. kljp@mit.edu

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Leonard, E., Runguphan, W., O'Connor, S. et al. Opportunities in metabolic engineering to facilitate scalable alkaloid production. Nat Chem Biol 5, 292–300 (2009). https://doi.org/10.1038/nchembio.160

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