Exploring the Microbiome-Wide Lysine Acetylation, Succinylation, and Propionylation in Human Gut Microbiota

Lysine acylations are important post-translational
modifications
that are present in both eukaryotes and prokaryotes and regulate diverse
cellular functions. Our knowledge of the microbiome lysine acylation
remains limited due to the lack of efficient analytical and bioinformatics
methods for complex microbial communities. Here, we show that the
serial enrichment using motif antibodies successfully captures peptides
containing lysine acetylation, propionylation, and succinylation from
human gut microbiome samples. A new bioinformatic workflow consisting
of an unrestricted database search confidently identified >60,000
acetylated, and ∼20,000 propionylated and succinylated gut
microbial peptides. The characterization of these identified modification-specific
metaproteomes, i.e., meta-PTMomes, demonstrates that lysine acylations
are differentially distributed in microbial species with different
metabolic capabilities. This study provides an analytical framework
for the study of lysine acylations in the microbiome, which enables
functional microbiome studies at the post-translational level.