# Identification of DELLA and GID1 genes in Catharanthus roseus and their potential role in regulating vindoline biosynthesis

## TL;DR

This study explores how DELLA and GID1 genes in Catharanthus roseus might influence the production of important chemotherapy drugs like vinblastine and vincristine.

## Contribution

The study provides initial evidence that CrDELLA genes may positively regulate vindoline biosynthesis in Catharanthus roseus.

## Key findings

- Silencing CrDELLA reduced vindoline pathway gene expression, while silencing CrGID1 increased alkaloid accumulation.
- Overexpression of truncated CrDELLAs increased promoter activity of vindoline pathway genes.
- Paclobutrazol treatment supported a potential role for CrDELLAs in activating vindoline biosynthesis.

## Abstract

DELLAs are key regulators of plant growth and development, negatively regulating gibberellic acid (GA) signaling and positively regulating light and jasmonate signaling and juvenile leaf development. In the presence of GA, GID1s bind to DELLAs and signal for their degradation. Here, we identified and characterized DELLA and GID1 genes in Catharanthus roseus, the natural source of chemotherapy drugs vinblastine and vincristine. We hypothesized that CrDELLAs positively regulate vindoline biosynthesis, a precursor of vinblastine and vincristine, accumulating in light- and jasmonate-exposed young leaves. To explore this hypothesis, we silenced CrDELLA or CrGID1 genes using virus-induced gene silencing. CrDELLA-silenced plants were elongated while CrGID1-silenced plants were dwarfed, consistent with their roles in GA-mediated growth. In the first experiment, CrDELLA-silencing significantly decreased vindoline pathway gene expression while CrGID1-silencing significantly increased vindoline, catharanthine, ajmalicine, and serpentine accumulation. However, subsequent experiments found little to no effect. C. roseus seedlings treated with paclobutrazol, an inhibitor of GA biosynthesis shown to increase DELLA protein stability, also provided some evidence for CrDELLA’s positive role in regulating vindoline pathway gene expression. Finally, overexpressed stabilized, N-terminal truncated CrDELLAs in C. roseus seedlings yielded significant increases in vindoline pathway promoter activity (NMT, D4H). Overall, these experiments provide weak to moderate evidence for CrDELLAs positively regulating vindoline biosynthesis. Future experiments with transgenic approaches could strengthen the evidence and clarify this relationship. Activation of the vindoline pathway with stabilized CrDELLAs could increase the production of critical chemotherapeutics, vinblastine and vincristine.

The online version contains supplementary material available at 10.1007/s11103-025-01599-1.

Transient silencing of CrDELLAs and CrGID1s, overexpression of truncated CrDELLAs, and application of the gibberellic acid-inhibitor paclobutrazol provide weak to moderate evidence that CrDELLAs activate vindoline biosynthesis in Catharanthus roseus.

The online version contains supplementary material available at 10.1007/s11103-025-01599-1.