Puzzling Out the Colchicine Biosynthetic Pathway. (9th November 2020)

• Record Type: Journal Article
• Authors: Stander, Emily A.; Papon, Nicolas; Courdavault, Vincent
• Is Part Of: ChemMedChem. Volume 16:Number 4(2021)
• Page Start: 621
• Page End: 623
• Publication Date: 2020-11-09
• Subjects: bio-production -- cell factories -- colchicine -- metabolic engineering -- tobacco; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000633
• Languages: English
• ISSNs: 1860-7179

Abstract

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. Abstract : Pick & mix : Recently, eight colchicine biosynthetic genes from G. superba, a natural colchicine‐producing plant, were elucidated by using a combination of transcriptomics, metabolomics and pathway reconstitution. These genes were subsequently used to engineer a biosynthetic pathway constituting a total of 16 enzymes in N. benthamiana to produce the colchicine precursor, N ‐formyldemecolcine, from amino acids phenylalanine and tyrosine.