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Puzzling Out the Colchicine Biosynthetic Pathway

Author

ChemMedChem. 2021 Feb 17;16(4):621-623. doi: 10.1002/cmdc.202000633.Epub 2020 Nov 9.

Emily A Stander 1Nicolas Papon 2 3Vincent Courdavault 1

Author Information

1 Université de Tours, BBV EA2106, 37200, Tours, France.

2 Host-Pathogen Interaction Study Group, Université Angers, GEIHP EA 3142, 49933, Angers, France.

3 Federative Structure of Research, Cellular Interactions and Therapeutic Applications, Université Angers, SFR 4208 ICAT, 49933, Angers, France.

Abstract

Colchicine is among the oldest plant natural products (NPs) still used for treating a broad spectrum of human diseases including gout and other articular inflammation disorders. This molecule is synthesized by several herbaceous species related to the Liliaceae family, but in very low quantities in whole plants. As for many pharmaceutical compounds from plants, the production of colchicine still depends on the natural resource from which it is extracted. From the past decade, metabolic engineering has progressively become a credible alternative for the cost-effective large-scale production of several valuable NPs. In the same vein, Nett and colleagues recently reported an unprecedented advance in the field for colchicine. By using a combination of transcriptomics, metabolomics and pathway reconstitution, Sattely's group deciphered a near-complete biosynthetic pathway to colchicine without prior knowledge of biosynthetic genes. Besides constituting a benchmark for the elucidation of natural product biosynthetic pathways, it opens unprecedented perspectives regarding metabolic engineering of colchicine biosynthesis.