dbPUP

dbPUP curates experimentally characterized polyphenol utilization proteins (PUPs) and their homologs to support analysis of polyphenol metabolism in the human gut microbiome.

Key Features:

• Curated Data Collection: Contains 60 manually curated PUP "seed" proteins from published literature annotated with species and substrate metadata.
• Extensive Homolog Identification: Identified 107,851 homologs across UniProt and the Unified Human Gastrointestinal Protein (UHGP) database to expand taxonomic and functional coverage.
• Systematic Classification: Classifies seeds and homologs into classes, families, and subfamilies using Enzyme Commission (EC) numbers, Pfam domains, and sequence similarity networks.
• Gene Cluster Analysis: Detects 1,074 physically linked PUP gene clusters (PGCs) within UHGP genomes.
• Geographical Insights: Reports higher abundance and prevalence of PUP homologs and PGCs in African gut microbiomes relative to other continents.
• Case Study Validation: Includes a Hadza hunter-gatherer microbiome case study demonstrating profiling of metagenomic data and diet–PUP abundance associations.
• Novel Family Identification: Uses Pfam domain enrichment analysis of PGCs to identify candidate novel PUP families.

Scientific Applications:

• Health Research: Facilitates investigation of how PUP-mediated polyphenol metabolism influences diseases such as cardiovascular conditions, cancers, and metabolic disorders.
• Microbiome Studies: Enables comparative analysis of functional capabilities of gut microbiota across populations.
• Dietary Interventions: Supports studies linking dietary variation to polyphenol metabolism and potential dietary recommendations.

Methodology:

Literature curation and database searches of UniProt and UHGP followed by bioinformatics analyses integrating Enzyme Commission (EC) numbers, Pfam domain annotation, and sequence similarity networks.