The vast majority of microbial diversity remains unculturable, limiting access to novel biotechnological resources. Advances in metagenomics have expanded the understanding of microbial communities, yet targeted protein discovery remains challenging. This study introduces ProteoSeeker, a command‐line tool for streamlined metagenomic protein identification and annotation. ProteoSeeker operates in two primary modes: i) Seek mode, which screens the proteins according to user‐defined protein families, and ii) Taxonomy mode, which uncovers the taxonomy of the host organisms. By automating key steps, ProteoSeeker reduces computational complexity, enabling time‐efficient and comprehensive metagenomic analysis for both specialized and nonspecialized users. The efficiency of ProteoSeeker to achieve targeted enzyme discovery is demonstrated by identifying extremophilic enzymes with desired biochemical features, such as amylases for starch hydrolysis and carbonic anhydrases for CO₂ capture applications. By democratizing functional metagenomics, ProteoSeeker is anticipated to accelerate biotechnology, synthetic biology, and biomedical research and innovation.

Receptor tyrosine kinases (RTKs) form a highly important group of protein receptors of the eukaryotic cell membrane. They control many vital cellular functions and are involved in the regulation of complex signaling networks. Mutations in RTKs have been associated with different types of cancers and other diseases. Although they are very important for proper cell function, they have been experimentally studied in a limited range of eukaryotic species. Currently, there is no available database for RTKs providing information about their function, expression, and interactions. Therefore, the identification of RTKs in multiple organisms, the documentation of their characteristics, and the collection of related information would be very useful. In this paper, we present a novel RTK detection pipeline (RTK-PRED) and the Receptor Tyrosine Kinases Database (TyReK-DB). RTK-PRED combines profile HMMs with transmembrane topology prediction to identify and classify potential RTKs. Proteins of all eukaryotic reference proteomes of the UniProt database were used as input in RTK-PRED leading to a filtered dataset of 20,478 RTKs. Based on the information collected for these RTKs from multiple databases, the relational TyReK database was created.

Metagenomics have served as a key driver of biotechnology advancements through, among others, the identification of novel proteins. The lack of standardized guidelines and benchmarks in the field, however, complicates the selection of appropriate bioinformatics tool ensembles and hinders faster progress. This study introduces ProteoSeeker , an automated pipeline designed for accessible and comprehensive metagenomic exploration of whole-genome sequencing data. ProteoSeeker identifies proteins within user-defined protein families and uncovers the taxonomy of the host organisms. It is implemented as a command-line tool to facilitate metagenomic dataset analysis for non-expert users, thus enabling facilitated and streamlined protein discovery.