# Elucidating the genetic basis of imidazopyrazinone luciferin biosynthesis for the development of improved bioluminescence imaging technologies

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $65,310

## Abstract

Project Summary / Abstract
Coelenterazine and vargulin are naturally-occurring imidazopyrazinone luciferins used in
bioluminescence imaging, but their scarcity and need to supply them exogenously to cell culture
and animal models limit their use. I propose to elucidate the biosynthesis of these compounds in
bioluminescent zooplankton. In Specific Aim 1, I discuss the possible biosynthetic origins for
these molecules, and my plans to identify the genes coding for the requisite biosynthetic
enzymes. In Specific Aim 2, I describe how I would apply these newly-discovered genes to
economically produce coelenterazine by fermentation in S. cerevisiae, addressing a critical
barrier to progress. In Specific Aim 3, I propose initial experiments to assess whether the ability
to effect the luciferin’s biosynthesis in human cell culture model improves bioluminescence
imaging contrast. Successful completion of this project could have revolutionary impacts on
biological imaging, akin to how development of Green Fluorescent Protein from a biological
curiosity into a multipurpose biochemical marker has radically transformed the way we apply
microscopy and imaging to biological questions. Besides improving imaging signal-to-noise,
localized in situ luciferin production in cell culture could aid research into inter- and intracellular
signaling. Moreover, expression of the luciferin biosynthetic machinery in animals would allow
for long-term noninvasive in vivo bioluminescence experiments such as gene expression
monitoring and assessing tumor burden in cancer disease models.

## Key facts

- **NIH application ID:** 9979650
- **Project number:** 5F32GM129960-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Tristan de Rond
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2018-08-15 → 2021-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979650

## Citation

> US National Institutes of Health, RePORTER application 9979650, Elucidating the genetic basis of imidazopyrazinone luciferin biosynthesis for the development of improved bioluminescence imaging technologies (5F32GM129960-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9979650. Licensed CC0.

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