Exploration of lysine acyl modifications derived from food ingredients

Abstract

Various lysine acyl modifications are related to epigenetic gene expression and are responsible for regulation of diverse biological phenomena. Lysine acylations occur depending on acyl-CoA derived from endogenous carboxylic acids. We are daily exposed to various carboxylic acids in the environments. We hypothesized that when these compounds are taken into the body, they may modify histones in a similar way to endogenous fatty acids, thereby altering gene expression and affecting health. Therefore, we developed a simple and efficient assay system to explore for histone modifiers among the myriad of carboxylic acids in our living environment, utilizing the interaction between acylated histones and reader proteins. Using this assay system, we searched for carboxylic acids with high consumption and found that several compounds have histone-modifying ability. Among them, we focused on aspartame, which is widely used as a sweetener, and examined changes in gene expression induced by aspartame. However, RNA-seq analysis revealed that aspartame had little effect on gene expression. These results suggest that histones may not be the primary target of aspartame modification. Indeed, analyses using alkyne-labeled aspartame derivatives suggest the presence of numerous proteins in cells that can be modified by aspartame. In this presentation, we would like to introduce our efforts to comprehensively search for proteins modified by aspartame using chemical biology approaches.