Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Post Bellary Road, Bangalore, India.
Section on Nutrient Control of Gene Expression, Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
Nat Commun. 2024 Aug 23;15(1):7254. doi: 10.1038/s41467-024-51769-w.
Cells contain disparate amounts of distinct amino acids, each of which has different metabolic and chemical origins, but the supply cost vs demand requirements of each is unclear. Here, using yeast we quantify the restoration-responses after disrupting amino acid supply, and uncover a hierarchically prioritized restoration strategy for distinct amino acids. We comprehensively calculate individual amino acid biosynthetic supply costs, quantify total demand for an amino acid, and estimate cumulative supply/demand requirements for each amino acid. Through this, we discover that the restoration priority is driven by the gross demand for an amino acid, which is itself coupled to low supply costs for that amino acid. Demand from metabolic requirements dominate the demand-pulls for an amino acid, as exemplified by the largest restoration response upon disrupting arginine supply. Collectively, this demand-driven framework that drives the amino acid economy can identify novel amino acid responses, and help design metabolic engineering applications.
细胞中含有不同数量的不同氨基酸，每种氨基酸都有不同的代谢和化学起源，但每种氨基酸的供应成本与需求要求尚不清楚。在这里，我们使用酵母来量化氨基酸供应中断后的恢复响应，并揭示了不同氨基酸的层次化优先恢复策略。我们全面计算了单个氨基酸生物合成的供应成本，量化了每种氨基酸的总需求，并估计了每种氨基酸的累积供应/需求要求。通过这种方法，我们发现恢复优先级是由氨基酸的总需求驱动的，而氨基酸的总需求又与该氨基酸的低供应成本相关。代谢需求决定了氨基酸的需求拉力，例如，破坏精氨酸供应时会产生最大的恢复响应。总的来说，这种由需求驱动的氨基酸经济框架可以识别新的氨基酸反应，并有助于设计代谢工程应用。
