# Multi‐omic analysis reveals genes and proteins integral to bioactivity of Echinochrome A isolated from the waste stream of the sea urchin industry in Aotearoa New Zealand

## TL;DR

This study uses genomic and proteomic methods to uncover how Echinochrome A, a compound from sea urchin waste, affects yeast cells, revealing its potential as a pharmaceutical.

## Contribution

The paper introduces an unbiased multi-omic approach to study Echinochrome A's bioactivity for the first time.

## Key findings

- Echinochrome A alters DNA replication, repair, and RNA binding in yeast cells within 30 minutes.
- The compound chelates iron, and iron supplementation reduces its growth-inhibiting effects.
- Genes related to oxidative stress, cardiolipin, and inositol phosphate biosynthesis are crucial for Ech A's bioactivity.

## Abstract

Evechinus chloroticus (commonly known as kina) is a sea urchin species endemic to New Zealand. Its roe is a culinary delicacy to the indigenous Māori and a globally exported food product. Echinochrome A (Ech A) is a bioactive compound isolated from the waste product of kina shells and spines; however, the molecular mechanisms of Ech A bioactivity are not well understood, partly due to Ech A never being studied using unbiased genome‐wide analysis. To explore the high‐value pharmaceutical potential of kina food waste, we obtained unbiased functional genomic and proteomic profiles of yeast cells treated with Echinochrome A. Abundance was measured for 4100 proteins every 30 min for four hours using fluorescent microscopy, resulting in the identification of 92 proteins with significant alterations in protein abundance caused by Ech A treatment that were over‐represented with specific changes in DNA replication, repair and RNA binding after 30 min, followed by specific changes in the metabolism of metal ions (specifically iron and copper) from 60–240 min. Further analysis indicated that Ech A chelated iron, and that iron supplementation negated the growth inhibition caused by Ech A. Via a growth‐based genome‐wide analysis of 4800 gene deletion strains, 20 gene deletion strains were sensitive to Ech A in an iron‐dependent manner. These genes were over‐represented in the cellular response to oxidative stress, suggesting that Ech A suppressed growth inhibition caused by oxidative stress. Unexpectedly, genes integral to cardiolipin and inositol phosphate biosynthesis were required for Ech A bioactivity. Overall, these results identify genes, proteins, and cellular processes mediating the bioactivity of Ech A. Moreover, we demonstrate unbiased genomic and proteomic methodology that will be useful for characterizing bioactive compounds in food and food waste.

The mechanism of action of Echinochrome A (Ech A) was evaluated using unbiased genomic and proteomic analyses.Growth analyses of gene deletions and measurements of protein abundance identified the importance of 20 genes and 92 proteins.The antioxidant activity of Ech A may begin with alterations in DNA replication, followed by iron chelation and disrupted cardiolipin metabolism.

The mechanism of action of Echinochrome A (Ech A) was evaluated using unbiased genomic and proteomic analyses.

Growth analyses of gene deletions and measurements of protein abundance identified the importance of 20 genes and 92 proteins.

The antioxidant activity of Ech A may begin with alterations in DNA replication, followed by iron chelation and disrupted cardiolipin metabolism.