Substrate space analysis of the bacterial proton-coupled oligopeptide transporter YdgR by cheminformatics.

Proton-dependent oligopeptide transporters (POTs) are recognized for their substrate promiscuity due to their ability to transport a wide range of substrates. POTs are conserved in all forms of life ranging from bacteria to humans. A dipeptide-fluorophore conjugate, H-(ß-Ala)-Lys(AMCA)-OH, is a well-known substrate of the transporter YdgR that is commonly used as a fluorescent reporter. In order to understand the substrate space of YdgR, we used this dipeptide as a bait reference, when screening an ensemble of compounds (previously tested in PEPT/PTR/NPF space) via a cheminformatic analysis based on the Tanimoto similarity index. Eight compounds (sinalbin, abscisic acid, carnosine, jasmonic acid, N-acetyl-aspartate, N-acetyl-lysine, aspartame, and N-acetyl-aspartylglutamate), covering a wide range on the Tanimoto scale, were tested for YdgR-mediated transport. Carnosine was the only compound observed to be a YdgR substrate based on cell-based transport assays and molecular docking. The other compounds tested were neither inhibitors nor substrates. Thus, we found that neither the Tanimoto similarity index nor ADME (absorption, distribution, metabolism, and excretion) properties appear useful for the identification of substrates (e.g., dipeptides) in YdgR-mediated drug transport.

Current State of SLC and ABC Transporters in the Skin and Their Relation to Sweat Metabolites and Skin Diseases.

With a relatively large surface area (2 m2) and 15% of total body mass, the skin forms the largest organ of the human body. The main functions of the skin include regulation of body temperature by insulation or sweating, regulation of the nervous system, regulation of water content, and protection against external injury. To perform these critical functions, the skin encodes genes for transporters responsible for the cellular trafficking of essential nutrients and metabolites to maintain cellular hemostasis. However, the knowledge on the expression, regulation, and function of these transporters is very limited and needs more work to elucidate how these transporters play a role both in disease progression and in healing. Furthermore, SLC and ABC transporters are understudied, and even less studied in skin. There are sparse reports on relation between transporters in skin and sweat metabolites. This mini review focuses on the current state of SLC and ABC transporters in the skin and their relation to sweat metabolites and skin diseases.

BeerMIMS: Exploring the Use of Membrane-Inlet Mass Spectrometry (MIMS) Coupled to KNIME for the Characterization of Danish Beers.

Beer is a complex mix of more than 7700 compounds, around 800 of which are volatile. While GC-MS has been actively employed in the analysis of the volatome of beer, this method is challenged by the complex nature of the sample. Herein, we explored the possible of using membrane-inlet mass spectrometry (MIMS) coupled to KNIME to characterize local Danish beers. KNIME stands for Konstanz Information Miner and is a free open-source data processing software which comes with several prebuilt nodes, that, when organized, result in data processing workflows allowing swift analysis of data with outputs that can be visualized in the desired format. KNIME has been shown to be promising in automation of large datasets and requires very little computing power. In fact, most of the computations can be carried out on a regular PC. Herein, we have utilized a KNIME workflow for data visualization of MIMS data to understand the global volatome of beers. Feature identification was not possible as of now but with a combination of MIMS and a KNIME workflow, we were able to distinguish beers from different micro-breweries located in Denmark, laying the foundation for the use of MIMS in future analysis of the beer volatome.