BANRETI

One of the most fascinating and unexplored questions in the life sciences is the origin and significance of biomolecular homochirality, a key feature that distinguishes all living organisms from inorganic/abiotic matter. Our interdisciplinary team aims to understand how organisms actively maintain the homochirality of their proteins. Specifically, we focus on identifying genes and mechanisms that regulate chirality by repairing post-translationally epimerized amino acid residues in proteins or eliminating heterochiral proteins. Our integrative research also seeks to uncover the mechanisms behind the direct pathological consequences of losing proteome homochirality in vivo.

Figure 1. Enzymatic repair of post-translationally epimerized residues ensures the maintenance of protein homochirality.

We have developed various methods and tools to monitor chirality changes and identify proteins with non-L-amino acids formed post-translationally through epimerization or isomerization in vivo, using Drosophila as a pilot model system. To understand the physiological relevance of homochirality regulation, we experimentally enhance heterochirality and investigate the molecular mechanisms underlying the physiological consequences of accumulating non-L-amino acid-containing proteins (Aim 1). We aim to map epimerization sites in evolutionarily conserved proteins using chiral-selective large-scale proteomics, bioinformatics, and AI-driven machine learning approaches (Aim 2). To understand how proteome L-homochirality is maintained in living organisms, we combine interdisciplinary chiral-selective techniques (analytical chemistry, physicochemistry) with genetic screening to identify chirality-regulating genes dedicated to preserving homochirality (Aim 3).

Figure 2. Far-UV Synchrotron Radiation Circular Dichroism (SRCD) spectra of homochiral and heterochiral pentamer peptides that were used as epitopes for chiral-selective antibody generation.