Department of Food Science, Cornell University, Ithaca, New York, USA.
Calico Life Sciences LLC, South San Francisco, California, USA.
Yeast. 2024 Jan;41(1-2):5-18. doi: 10.1002/yea.3910. Epub 2023 Nov 23.
Auxotrophic strains starving for their cognate nutrient, termed auxotrophic starvation, are characterized by a shorter lifespan, higher glucose wasting phenotype, and inability to accomplish cell cycle arrest when compared to a "natural starvation," where a cell is starving for natural environmental growth-limiting nutrients such as phosphate. Since evidence of this physiological response is limited to only a subset of auxotrophs, we evaluated a panel of auxotrophic mutants to determine whether these responses are characteristic of a broader range of amino acid auxotrophs. Based on the starvation survival kinetics, the panel of strains was grouped into three categories-short-lived strains, strains with survival similar to a prototrophic wild type strain, and long-lived strains. Among the short-lived strains, we observed that the tyrosine, asparagine, threonine, and aspartic acid auxotrophs rapidly decline in viability, with all strains unable to arrest cell cycle progression. The three basic amino acid auxotrophs had a survival similar to a prototrophic strain starving in minimal media. The leucine, tryptophan, methionine, and cysteine auxotrophs displayed the longest lifespan. We also demonstrate how the phenomenon of glucose wasting is limited to only a subset of the tested auxotrophs, namely the asparagine, leucine, and lysine auxotrophs. Furthermore, we observed pleiotropic phenotypes associated with a subgroup of auxotrophs, highlighting the importance of considering unintended phenotypic effects when using auxotrophic strains especially in chronological aging experiments.
营养缺陷型菌株在其同源营养物质饥饿时，被称为营养缺陷型饥饿，与“自然饥饿”相比，其具有寿命更短、葡萄糖浪费表型更高以及无法完成细胞周期停滞的特征，“自然饥饿”是指细胞因缺乏自然环境中的生长限制营养物质（如磷酸盐）而饥饿。由于这种生理反应的证据仅限于少数营养缺陷型菌株，因此我们评估了一组营养缺陷型突变株，以确定这些反应是否是更广泛范围的氨基酸营养缺陷型的特征。基于饥饿存活动力学，将该组菌株分为三类：寿命短的菌株、与野生型原养型菌株存活相似的菌株和寿命长的菌株。在寿命短的菌株中，我们观察到色氨酸、天冬酰胺、苏氨酸和天冬氨酸营养缺陷型菌株的活力迅速下降，所有菌株均无法阻止细胞周期进程。三种碱性氨基酸营养缺陷型菌株的存活与在最小培养基中饥饿的野生型原养型菌株相似。亮氨酸、色氨酸、甲硫氨酸和半胱氨酸营养缺陷型菌株具有最长的寿命。我们还展示了葡萄糖浪费现象如何仅限于仅测试的营养缺陷型菌株的一部分，即天冬酰胺、亮氨酸和赖氨酸营养缺陷型菌株。此外，我们观察到与营养缺陷型菌株的亚群相关的多效表型，强调了在使用营养缺陷型菌株特别是在定时老化实验中，考虑意外表型效应的重要性。
