Recent progress in the metabolic engineering of alkaloids in plant systems

Plant alkaloids have a rich chemical ecology that has been exploited for medicinal purposes for thousands of years. Despite being highly represented within today's pharmacopoeia, relatively little is known about the biosynthesis, regulation and transport of these molecules. Understanding how nature synthesizes plant alkaloids will enhance our ability to overproduce—that is, to metabolically engineer—these medicinally useful compounds as well as new-to-nature compounds (with potentially improved bioactivity) derived from these natural scaffolds. Recent progress in the metabolic engineering of nitrogen-containing plant natural products—specifically the monoterpene indole alkaloids, the benzylisoquinoline alkaloids and the glucosinolates—was made possible through the characterization of various components in both native and engineered enzymatic pathways. The subsequent reconfiguration and tuning of these biological ‘parts’ has enabled the production of selected products at increasingly higher titers.

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► Recent metabolic engineering efforts for plant alkaloids.
► Characterizing, reconfiguring and fine-tuning metabolic ‘parts’ improves titers.
► Additional strategies are necessary to produce ‘unnatural’ natural products.