Biology subjects

Ahmad, M. S.

Publications and source records attributed to Ahmad, M. S..

3 recordsLinked to original sources

bioRxiv2025

Quantitative, temporal dynamics of the cellular amino acid economy reveals public vs private goods and enables syntrophic yeast community design.

The biosynthetic capacity of the cell governs the production and exchange of amino acids. Amino acids have diverse metabolic origins and intracellular requirements. Therefore, to understand the cellular amino acid economy we require a quantitative understanding of intracellular and extracellular their amounts, and how distinct amino acids change temporally during growth. Using the unicellular eukaryote, yeast, we establish a quantitative blueprint of the intracellular and extracellular amino acid economy, including the fluxes of production, secretion and consumption across different growth phases. Certain amino acids dominate the intracellular pool, and proportions of distinct amino acids continuously change during growth. The extracellular pool is notably distinct from the intracellular pool in terms of composition and dynamics. Only some public amino acids are subsequently consumed, while others are secreted in surplus of cellular demands. Five amino acids are intracellular and privatized, and continuously utilized to support diverse metabolism. Through this, we establish pairs of highly effective synthetic, exchange-based communities of public good auxotrophs. Our results suggest organizing frameworks addressing the dynamic intracellular and inter-cellular amino acid economy and its trade, and informs the rational engineering of syntrophic cell communities.

systems biology↗

bioRxiv2025

Plasma membrane folate transport in fungi and plants is mediated by members of the oligopeptide transporter (OPT) family

Folates are essential for all organisms. They are acquired either through de novo biosynthesis or from the diet. Yeast, fungi and plants make their own folates and it has not been clear if plasma membrane folate transporters exist in these organisms. Using a synthetic lethal screen in Saccharomyces cerevisiae we observed that deletions in a gene encoding the previously identified glutathione transporter, OPT1, was synthetically sick with a disruption in folate biosynthesis. Uptake experiments confirmed that Opt1p/Hgt1p can transport folinic acid and the naturally abundant methyl tetrahydrofolate. As S. cerevisiae Opt1p was able to transport both folate and glutathione, we used alanine-scanning mutants of the residues in the transmembrane domains of the channel to identify the residues required specifically for the uptake of folates and distinct from those required for glutathione. We further examined the oligopeptide transporter family of other organisms for the presence of folate transporters. In C. albicans, CaOPT1, the orthologue of S. cerevisiae OPT1 efficiently transported folate but not glutathione, while the previously characterized glutathione transporter, CaOPT7 could not transport folate. Aspergillus fumigatus has eight homologues of the oligopeptide transporter family, of which OptB and OptH could transport folates. In the plant Arabidopsis thaliana, the Opt1 homologs AtOpt2, AtOpt4, and AtOpt6 could transport folates. This discovery of folate transporters across fungi and plants fills a critical gap in our understanding of folate metabolism, and can benefit the exploitation of these pathways in pathogenic fungi, and in plants.

genetics↗

bioRxiv2025

Seo1p, a high affinity, plasma membrane transporter of the gamma-Glu-met dipeptide in yeasts and fungi

{gamma}-Glu dipeptides are ubiquitous in nature, and yet their metabolism and transport are poorly understood. Here we investigate this using the dipeptide {gamma}-Glu-met in Saccharomyces cerevisiae. {gamma}-Glu-met was efficiently utilized by S. cerevisiae and its degradation was dependent on both the glutathione degrading cytosolic Dug2p/Dug3p complex, and the vacuolar Ecm38p. Using a transcriptomics approach, followed by a genetic screen, we identified Seo1p, an orphan transporter of yeast, as the transporter of {gamma}-Glu-met. Uptake studies confirmed Seo1p as a high affinity (Km =48uM), highly specific transporter of {gamma}-Glu-met since other analogs like n-Glu-met, {gamma}-Glu-leu, {gamma}-Glu-cys, {gamma}-Glu-met-gly, methionine and methionine sulfoxide were not transported by Seo1p. Candida spp. also encoded a functional Seo1p. A second transporter, Opt2p, identified in the screen, was also investigated. However, Opt2p was not primarily involved in {gamma}-Glu-met uptake. Its deletion affected vacuolar morphology, that interfered with the degradation of the peptide through Ecm38p. These studies demonstrate how organisms have evolved dedicated pathways for the uptake of these unusual peptides.

genetics↗