Project description:Lysine lactylation (Kla) is a newly discovered histone post-translational modification (PTM), playing important roles in regulating transcription in macrophages. Increasing evidence demonstrates that lysine lactylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine lactylation in fungi, here investigated with the black yeast Phialophora verrucosaverrucose as a model organism. WeHere, we report the first proteomic survey of this modification in P. verrucosa. We performed a global lactylation analysis of P. verrucosa using high accuracy bottom-up nano-LC-MS/MS in combination wwith the enrichment of lactylated peptides from digested cell lysates and subsequent peptide identification. In total, 636 lactylation sites on 420 lactylated proteins were identified in this pathogen, of which contained in 26 types of modification motifs. Our results show that over 85% of lactylated proteins were distributed in cytoplasm, mitochondria, and nucleus. The identified proteins were found to be involved associated toin diverse biological processes and were significantly enriched in the melanin biosynthesis process. Most strikingly, Kla was found in 23 structural constituent proteins of ribosome, indicating an impact of Kla in protein synthesis . Moreover, 12 lactylated proteins participated in fungal pathogenicity, suggesting a potential role for Kla in this process. Protein interaction network analysis suggested that a mass of protein interactions are regulated by lactylation. Together, our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in P. verrucosa. Our data provide a rich resource for functional analyses of lactylation and facilitate the dissection of metabolic networks in this pathogen. The combined data sets represent the first report of the lactylome of P. verrucosa and provide a good foundation for further explorations of Kla in clinical fungal pathogens.
Project description:Lactylation at lysine residue (Klac) modification is a novel PTM first discovered on histones in mammalian cells in 2019 [8]. It has been observed that Klac modification on histones modulates macrophage polarization and state, and influences cellular metabolic reprogramming in pluripotent stem cells and nonsmall cell lung cancer, and can even induce tumorigenesis [5,6]. Subsequent investigations have shown that Klac modification extends to non-histone proteins in various subcellular compartments and proteins in prokaryotic cells. To date, Klac modification has been extensively identified in various organisms, including humans [8,10-17], mice [18-20], rats [16], insects [21], plants (rice [22] and wheat [23]), fungi (Botrytis cinerea [24] and Phialophora verrucosa [25]), algae (Nannochloropsis oceanica [26]), parasites (Toxoplasma gondii [27] and Trypanosoma brucei [28]), and bacteria (Escherichia coli [5] and Streptococcus mutans [6]). These studies collectively demonstrate the evolutionary conservation of Klac modification across diverse organisms.
