Metabolomics analysis reveals both plant variety and choice of hormone treatment modulate vinca alkaloid production in Catharanthus roseus.

Valerie N Fraser,Molly Megraw,Benjamin Philmus

doi:10.1002/pld3.267

Abstract

The medicinal plant Catharanthus roseus produces numerous secondary metabolites of interest for the treatment of many diseases – most notably for the terpene indole alkaloid (TIA) vinblastine, which is used in the treatment of leukemia and Hodgkin's lymphoma. Historically, methyl jasmonate (MeJA) has been used to induce TIA production, but in the past, this has only been investigated in whole seedlings, cell culture, or hairy root culture. This study examines the effects of the phytohormones MeJA and ethylene on the induction of TIA biosynthesis and accumulation in the shoots and roots of 8‐day‐old seedlings of two varieties of C. roseus. Using LCMS and RT‐qPCR, we demonstrate the importance of variety selection, as we observe markedly different induction patterns of important TIA precursor compounds. Additionally, both phytohormone choice and concentration have significant effects on TIA biosynthesis. Finally, our study suggests that several early‐induction pathway steps as well as pathway‐specific genes are likely to be transcriptionally regulated. Our findings highlight the need for a complete set of'omics resources in commonly used C. roseus varieties and the need for caution when extrapolating results from one cultivar to another.

Highlights

Many plant-derived secondary metabolites have chemical properties that give them therapeutic value for the treatment of cancers, hypertension, and other illnesses (Balunas and Kinghorn, 2005)
Seedlings from each variety were treated with control treatment or methyl jasmonate (100 M) or ethephon (100 M or 1 mM) for 24 hours, and were subsequently divided at the hypocotyl
None of the studies included LBE and SunStorm Apricot” (SSA) which would allow for the utilization of available genomic and transcriptomic resources to inform future bioengineering efforts

Summary

Introduction

Many plant-derived secondary metabolites have chemical properties that give them therapeutic value for the treatment of cancers, hypertension, and other illnesses (Balunas and Kinghorn, 2005). The terpene indole alkaloid (TIA) family of natural products include many valuable medicinal compounds such as the clinically used antineoplastic agents vinblastine and vincristine, as well as the antihypertensive agent ajmalicine (Figure 1). Vinblastine and vincristine, used in the treatment of lymphoblastic leukemia (Noble et al, 1958; Johnson et al, 1963), are naturally produced at low levels in the leaves of the plant, which makes the chemical extraction of the two alkaloids difficult and time consuming (Tyler, 1988). While MeJA is too expensive for practical use in a large-scale agricultural production, ethephon (a commercially available ethylene derivative) is a viable and cost-effective option for increasing alkaloid yields prior to chemical extraction

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