Elucidating the enzyme network driving Amaryllidaceae alkaloids biosynthesis in Leucojum aestivum

Lamichhane, B., Gélinas, S.-E., Merindol, N., Koirala, M., dos Santos, K. C. G., Germain, H. et Desgagné-Penix, I. (2025). Elucidating the enzyme network driving Amaryllidaceae alkaloids biosynthesis in Leucojum aestivum. Plant Biotechnology Journal . ISSN 1467-7644 DOI 10.1111/pbi.70026

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Summary

Amaryllidaceae alkaloids (AAs) are diverse bioactive metabolites with significant pharmaceutical potential, derived from 4′-O-methylnorbelladine (4′OM). The biosynthesis of these compounds involves the condensation of tyramine and 3,4-dihydroxybenzaldehyde by norbelladine synthase (NBS) and/or noroxomaritidine/norcraugsodine reductase (NR), followed by O-methylation. Cytochrome P450 enzymes, particularly the CYP96T family, introduce further structural diversity through C–C couplings, resulting in lycorine, galanthamine and crinine cores. Despite their importance, the exact biosynthetic pathways remain poorly defined. In this study, we describe key enzymes from Leucojum aestivum (La), providing crucial insight into AA biosynthesis. Transient expression in Nicotiana benthamiana demonstrated that LaNBS and LaNRII catalyse the conversion of tyramine and 3,4-dihydroxybenzaldehyde to norbelladine, which is subsequently O-methylated by a norbelladine-4′-O-methyltransferase (LaN4′OMT) in planta. Co-agroinfiltration of LaNBS, LaNRII, LaN4′OMT and LaCYP96T1 resulted in the production of various phenol-coupled products, with lycorine as the predominant compound, alongside haemanthamine, crinine/vittatine and norgalanthamine. This study identifies LaCYP96T1 and LaCYP96T2 as the first monocot enzymes capable of catalysing all three regioselective C-C phenol couplings and also highlights the substrate promiscuity of LaNRII. The findings not only elucidate critical steps in AA biosynthesis but also open new avenues for biotechnological application in producing valuable alkaloids, offering potential for novel drug development.

Type de document:	Article
Date de dépôt:	25 mars 2025 17:29
Dernière modification:	25 mars 2025 17:29
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/11771

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