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

Abstract

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.