Functional Assessment of Orphan Proteins in the Streptomyces Pan-Proteome Through Genome-Wide Synteny Analysis

Members of the genus Streptomyces possess large genomes, a vast and largely unexplored metabolic potential, and a distinctive life cycle characterized by pronounced morphological differentiation. However, despite extensive molecular, genomic, and microbiological research, the functions of many genes in this genus remain poorly characterized. In this study, 929 complete Streptomyces genomes were analyzed. From the predicted proteomes of these genomes, proteins conserved in at least 75% of strains and lacking annotation in the KEGG GENES database were identified and clustered. To expand the annotation, synteny and co-occurrence analyses were performed between these unannotated proteins and annotated genes. A total of 330 conserved clusters were identified; 284 out of 330 clusters contain proteins encoded by genes that are syntenic with those associated with transcriptional regulation, fatty acid metabolism, two-component signaling systems, and morphological development. Additional clusters included metalloproteins and enzymes such as dehydrogenases, suggesting a wide functional spectrum. The conserved yet uncharacterized proteins identified in this analysis represent promising targets for future research, both for elucidating the molecular biology of Streptomyces and for expanding the range of secondary metabolites produced by these ecologically and industrially significant microorganisms.