Biosynthesis of Securinega alkaloids via a cyanogenic glucoside-like pathway
- 1University of York
Abstract
The elucidation of biosynthetic pathways towards bioactive compounds in plants is essential for building biotechnological platforms for their scalable synthesis. Securinine and allosecurinine form part of the complement of Securinega alkaloids in Flueggea suffruticosa, a fundamental herb of Chinese medicine. Despite their potent biological activities and a growing interest in derivatives as pharmaceutical leads, key steps in their biosynthesis remain obscure. Here we report the discovery and reconstitution of the pathway to the core Securinega alkaloid precursor menisdaurilide. Using transcriptomics, Nicotiana benthamiana transient expression, in vitro assays, and pathway reconstitution in Saccharomyces cerevisiae, we reveal that three cytochrome P450s and a reductase are required for the biosynthesis of menisdaurilide from L-tyrosine via the cyano-metabolite menisdaurigenin, revealing a surprising convergence with the biosynthesis of cyanogenic glucosides such as dhurrin. The de novo biosynthesis of allosecurinine in N. benthamiana highlights the potential for preparative-scale heterologous production of Securinega alkaloids.
Related
- Engineering the paclitaxel biosynthetic pathway in Physcomitrium patens for de novo and stable biosynthesis
- Two-step biosynthesis of benzyl alcohol from benzoyl-CoA within the phenylalanine-derived salicylic acid biosynthetic pathway in plants
- Metabolic Engineering of Saccharomyces cerevisiae for Betulinic Acid Biosynthesis Reveals Pitfalls of Mitochondrial Compartmentalization of the Mevalonate Pathway
- Comparative analysis of precursor supply and pathway reinforcement strategies for shikimic acid biosynthesis in Pseudomonas putida.
- Alkaloids Reported in the Genus Griffinia (Amaryllidaceae): Phytochemical Evidence and Current Limitations in Anticancer Interpretation
BibTeX
@misc{jiang2026biosynthesis,
title = {{Biosynthesis of Securinega alkaloids via a cyanogenic glucoside-like pathway}},
author = {Z. Jiang and L. J. N. Waddell and I. Amarnath and C. A. Hancock and O. R. Hughes and G. Grogan and W. P. Unsworth and B. R. Lichman},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.14.759206},
url = {https://www.biorxiv.org/content/10.64898/2026.10.14.759206v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Biosynthesis of Securinega alkaloids via a cyanogenic glucoside-like pathway
AU - Z. Jiang
AU - L. J. N. Waddell
AU - I. Amarnath
AU - C. A. Hancock
AU - O. R. Hughes
AU - G. Grogan
AU - W. P. Unsworth
AU - B. R. Lichman
PY - 2026
DA - 2026/10/14
PB - bioRxiv
DO - 10.64898/2026.10.14.759206
UR - https://www.biorxiv.org/content/10.64898/2026.10.14.759206v1
AB - The elucidation of biosynthetic pathways towards bioactive compounds in plants is essential for building biotechnological platforms for their scalable synthesis. Securinine and allosecurinine form part of the complement of Securinega alkaloids in Flueggea suffruticosa, a fundamental herb of Chinese medicine. Despite their potent biological activities and a growing interest in derivatives as pharmaceutical leads, key steps in their biosynthesis remain obscure. Here we report the discovery and reconstitution of the pathway to the core Securinega alkaloid precursor menisdaurilide. Using transcriptomics, Nicotiana benthamiana transient expression, in vitro assays, and pathway reconstitution in Saccharomyces cerevisiae, we reveal that three cytochrome P450s and a reductase are required for the biosynthesis of menisdaurilide from L-tyrosine via the cyano-metabolite menisdaurigenin, revealing a surprising convergence with the biosynthesis of cyanogenic glucosides such as dhurrin. The de novo biosynthesis of allosecurinine in N. benthamiana highlights the potential for preparative-scale heterologous production of Securinega alkaloids.
ER -