A catalogue of small proteins from the global microbiome

Duan, Yiqian; Santos-Junior, Celio Dias; Schmidt, Thomas Sebastian; Fullam, Anthony; de Almeida, Breno L. S.; Zhu, Chengkai; Michael, Kuhn; Zhao, Xing-Ming; Bork, Peer; Coelho, Luis Pedro

doi:10.1101/2023.12.27.573469

Cited by 2 publications

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Challenges in computational discovery of bioactive peptides in ’omics data

Coelho,

Santos‐Júnior,

de la Fuente‐Nunez

2024

Proteomics

Self Cite

View full text Add to dashboard Cite

Peptides have a plethora of activities in biological systems that can potentially be exploited biotechnologically. Several peptides are used clinically, as well as in industry and agriculture. The increase in available ’omics data has recently provided a large opportunity for mining novel enzymes, biosynthetic gene clusters, and molecules. While these data primarily consist of DNA sequences, other types of data provide important complementary information. Due to their size, the approaches proven successful at discovering novel proteins of canonical size cannot be naïvely applied to the discovery of peptides. Peptides can be encoded directly in the genome as short open reading frames (smORFs), or they can be derived from larger proteins by proteolysis. Both of these peptide classes pose challenges as simple methods for their prediction result in large numbers of false positives. Similarly, functional annotation of larger proteins, traditionally based on sequence similarity to infer orthology and then transferring functions between characterized proteins and uncharacterized ones, cannot be applied for short sequences. The use of these techniques is much more limited and alternative approaches based on machine learning are used instead. Here, we review the limitations of traditional methods as well as the alternative methods that have recently been developed for discovering novel bioactive peptides with a focus on prokaryotic genomes and metagenomes.

show abstract

Challenges in computational discovery of bioactive peptides in ’omics data

Coelho,

Santos‐Júnior,

de la Fuente‐Nunez

2024

Proteomics

Self Cite

View full text Add to dashboard Cite

show abstract

A cell-free system for functional studies of small membrane proteins

Jiang,

Çelen,

Glatter

et al. 2023

Preprint

View full text Add to dashboard Cite

Numerous small proteins have been discovered across all domains of life, among which many are hydrophobic and predicted to localize to the cell membrane. Based on a few that are well-studied, small membrane proteins are regulators involved in various biological processes, such as cell signaling, nutrient transport, drug resistance, and stress response. However, the function of most recently identified small membrane proteins remains elusive. Their small size and hydrophobicity make protein production challenging, hindering function discovery. Here, we combined a cell-free system with lipid sponge droplets and synthesized small membrane proteins in vitro. Lipid sponge droplets contain a dense network of lipid bilayers, which accommodates and extracts newly synthesized small membrane proteins from the aqueous surroundings. Using small bacterial membrane proteins MgrB and SafA as proof of principle, we showed that the in vitro produced membrane proteins reached sufficient concentrations for downstream analysis, and more importantly, they are functionally active. The cell-free system was also suitable for synthesizing other small membrane proteins, including one from human, indicating its high level of versatility. Furthermore, we showed that small proteins produced in this system can be used for in vitro pull-down assays to identify interaction partners. This work presents a robust alternative approach for producing small membrane proteins, which may aid their function discovery in all domains of life.

show abstract

A catalogue of small proteins from the global microbiome

Cited by 2 publications

References 76 publications

Challenges in computational discovery of bioactive peptides in ’omics data

Challenges in computational discovery of bioactive peptides in ’omics data

A cell-free system for functional studies of small membrane proteins

Contact Info

Product

Resources

About