Endogenous peptides and proteins are important nutrients in milk and important participants in various biological processes. In the present study, we compared endogenous peptides and parent proteins in bovine milk from different lactation stages using the 4D label-free technique. Endogenous peptides were identified by database search or de novo analysis. Through database searches, we matched 10186 endogenous peptides in bovine milk, which were derived from 1147 parent proteins. By de novo analysis, we identified a total of 1991 endogenous peptides. Among these peptides, 4852 differentially expressed endogenous peptides (DEEPs) between bovine colostrum (BC) and mature milk (BM) were found with various bioactivities, including ACE-inhibitory, immunomodulatory and anticancer activities. Gene Ontology (GO) annotation showed that the differentially expressed parent proteins between BC and BM were mainly in the structural molecule activity category within the molecular function subgroup. The primary Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was related to ribosomes. These results reveal the changes in the functions and activities of endogenous peptides and parent proteins in bovine milk during lactation and provide novel insight into developing infant formula powder based on bovine sources.
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