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BAHD news from Euphorbia peplus: identification of acyltransferase enzymes involved in ingenane diterpenoid biosynthesis

Schotte, C.; Florean, M.; Czechowski, T.; Gilday, A.; Alam, R.; Ploss, K.; Wurlitzer, J.; Li, Y.; Sonawane, P.; Graham, I. A.; O'Connor, S. E.

2025-03-11 biochemistry
10.1101/2025.03.03.641262 bioRxiv
Show abstract

O_LIThe plant family Euphorbiaceae are an abundant source of structurally complex diterpenoids, many of which have reported anti-cancer, anti-HIV, and anti-inflammatory activities. Among these, ingenol-3-angelate (1a; tradename: Picato(R)), isolated from Euphorbia peplus, has potent anti-tumour activity. C_LIO_LIHere we report the discovery and characterization of the first genes linked to the committed steps of ingenol-3-angelate (1a) biosynthesis in Euphorbia peplus. We identified two genes, the products of which catalyse the addition of angelyl-CoA (9a) to the ingenol (5) scaffold to produce ingenol-3-angelate (1a). C_LIO_LIWe demonstrate using VIGS that just one of these genes, EpBAHD-08, is essential for this angeloylation in E. peplus. VIGS of the second gene, EpBAHD-06, has a significant effect on jatrophanes rather than ingenanes in E. peplus. C_LIO_LIWe also identified three genes whose products can catalyse acetylation of ingenol-3-angelate (1a) to ingenol-3-angelate-20-acetate (2). In this case VIGS indicates considerable functional redundancy in the E. peplus genome of genes encoding this enzymatic step. C_LIO_LIThis work paves the way for increasing ingenol-3-angelate (1a) levels in planta and provides a foundation for the discovery of the remaining genes in the biosynthetic pathway of these important molecules. C_LI

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