Systematic Analysis of Lysine Lactylation in the Plant Fungal Pathogen Botrytis cinerea

Abstract

Lysine lactylation (Kla) is a newly discovered histone post-translational modification (PTM), playing important roles in regulating transcription in macrophages. However, the extent of this PTM in non-histone proteins remains unknown. Here, we report the first proteomic survey of this modification in Botrytis cinerea, a destructive necrotrophic fungal pathogen distributed worldwide. After a global lysine lactylome analysis using LC-MS/MS, we identified 273 Kla sites in 166 proteins, of which contained in 4 types of modification motifs. Our results show that the majority of lactylated proteins were distributed in nucleus (36%), mitochondria (27%), and cytoplasm (25%). The identified proteins were found to be involved in diverse cellular processes. Most strikingly, Kla was found in 43 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. The combined data sets represent the first report of the lactylome of B. cinerea and provide a good foundation for further explorations of Kla in plant fungal pathogens.

The Role of Posttranslational Modification and Mitochondrial Quality Control in Cardiovascular Diseases

“…In addition to binding to histones, lactylation can also occur on the sites of nonhistones. Gao et al found that lactylated proteins in Botrytis cinerea are mainly distributed in the nucleus, mitochondria, and cytoplasm, and are correlated with their pathogenicity through protein-protein interactions [ 136 ].…”

Protein Lactylation Critically Regulates Energy Metabolism in the Protozoan Parasite Trypanosoma brucei

“…Histone lactylation activates genes associated with the process of clearing infections ( Izzo and Wellen, 2019 ), and was therefore proposed as a mechanism for restoring tissue homeostasis. However, Kla in non-histone proteins has only been identified in plant fungal pathogens ( Gao et al, 2020 ). The function of lactylation in non-histone proteins in other organisms, especially in the early branching organisms, is not well understood.…”

Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects

“…Beyond histone protein modifications, a global lysine lactylome analysis was recently performed by LC-MS/MS in Botrytis cinerea , a devastating necrotizing fungal pathogen. There were 273 identified Kla sites from 166 proteins, and most proteins with lactylation had wide distribution, including the nucleus (36%), mitochondria (27%), and cytoplasm (25%) ( 89 ).…”

“…Citrate synthase is a rate-limiting enzyme in the TCA cycle and was found to be lactylated at K401. At multiple sites of two eukaryotic translation initiation factor 5A (eIF5a), proteins were modified by lactate ( 89 ). The protein interaction network demonstrated that lactylation could regulate interactions between proteins, highlighting the extensiveness of lactylation within cells.…”