Biosynthesis of Veratrum californicum specialty chemicals in Camelina sativa seed

• Published in: Plant biotechnology reports Vol. 11; no. 1; pp. 29 - 41
• Main Authors: Augustin, Megan M., Shukla, Ashutosh K., Starks, Courtney M., O’Neil-Johnson, Mark, Han, Linna, Holland, Cynthia K., Kutchan, Toni M.
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.02.2017; Springer Nature B.V; 한국식물생명공학회
• Subjects: Agriculture; Analysis; Bacteria; Biomedical and Life Sciences; Biosynthesis; Biotechnology; Camelina sativa; Cancer therapies; Cell Biology; Cloning; E coli; Escherichia coli; Fatty acids; FDA approval; Flowers & plants; Gene expression; Genes; Genetic engineering; Life Sciences; Metabolism; Metabolites; Natural products; Oilseeds; Original Article; Pharmacology; Plant Biochemistry; Plant Sciences; Saccharomyces cerevisiae; Secondary metabolites; Seeds; Steroids; Studies; Veratrum californicum; Yeast; 농학; Secondary metabolite; Verazine; Steroid alkaloid; Cyclopamine
• ISSN: 1863-5466; 1863-5474
• DOI: 10.1007/s11816-017-0427-x

Economically feasible systems for heterologous production of complex secondary metabolites originating from difficult to cultivate species are in demand since Escherichia coli and Saccharomyces cerevisiae are not always suitable for expression of plant and animal genes. An emerging oilseed crop, Camelina sativa , has recently been engineered to produce novel oil profiles, jet fuel precursors, and small molecules of industrial interest. To establish C. sativa as a system for the production of medicinally relevant compounds, we introduced four genes from Veratrum californicum involved in steroid alkaloid biosynthesis. Together, these four genes produce verazine, the hypothesized precursor to cyclopamine, a medicinally relevant steroid alkaloid whose analogs are currently being tested for cancer therapy in clinical trials. The future supply of this potential cancer treatment is uncertain as V. californicum is slow-growing and not amendable to cultivation. Moreover, the complex stereochemistry of cyclopamine results in low-yield syntheses. Herein, we successfully engineered C. sativa to synthesize verazine, as well as other V. californicum secondary metabolites, in seed. In addition, we have clarified the stereochemistry of verazine and related V. californicum metabolites.