Cell-Death Metabolites from Cocconeis scutellum var. parva Identified by Integrating Bioactivity-Based Fractionation and Non-Targeted Metabolomic Approaches

Abstract

Epiphytic diatoms growing in Mediterranean seagrass meadows, particularly those of the genus Cocconeis, are abundant and ecologically significant, even in naturally acidified environments. One intriguing aspect of some benthic diatoms is their production of an unidentified cell-death-promoting compound, which induces destruction of the androgenic gland in Hippolyte inermis Leach, 1816, a shrimp exhibiting protandric hermaphroditism, principally under normal environmental pH levels. The consumption of Cocconeis spp. by this shrimp is vital for maintaining the stability of its natural populations. Although many attempts have been made to reveal the identity of the apoptotic compound, it is still unknown. In this study, we strategically integrated a bioactivity-based fractionation, a metabolomic approach, and two different experimental avenues to identify potential apoptotic metabolites from Cocconeis scutellum var. parva responsible for the sex reversal in H. inermis. Our integrated analysis uncovered two potential candidate metabolites, one putatively identified as a lysophosphatidylglycerol (LPG) (16:1) and the other classified as a fatty acid ester. This is the first time LPG (16:1) has been reported in C. scutellum var. parva and associated with cell-death processes. These candidate metabolites mark substantial progress in elucidating the factors responsible for triggering the removal of the androgenic gland in the early post-larval phases of H. inermis.