Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
PLoS One. 2012;7(8):e42475. doi: 10.1371/journal.pone.0042475. Epub 2012 Aug 2.
As a key intracellular metabolite, acetyl-coenzyme A (acetyl-CoA) plays a major role in various metabolic pathways that link anabolism and catabolism. In the yeast Saccharomyces cerevisiae, acetyl-CoA involving metabolism is compartmentalized, and may vary with the nutrient supply of a cell. Membranes separating intracellular compartments are impermeable to acetyl-CoA and no direct transport between the compartments occurs. Thus, without carnitine supply the glyoxylate shunt is the sole possible route for transferring acetyl-CoA from the cytosol or the peroxisomes into the mitochondria. Here, we investigate the physiological profiling of different deletion mutants of ACS1, ACS2, CIT2 and MLS1 individually or in combination under alternative carbon sources, and study how various mutations alter carbon distribution. Based on our results a detailed model of carbon distribution about cytosolic and peroxisomal acetyl-CoA metabolism in yeast is suggested. This will be useful to further develop yeast as a cell factory for the biosynthesis of acetyl-CoA-derived products.
作为一种关键的细胞内代谢物，乙酰辅酶 A（acetyl-CoA）在连接合成代谢和分解代谢的各种代谢途径中起着重要作用。在酵母酿酒酵母中，涉及代谢的乙酰辅酶 A 被分隔在不同的隔室中，并且可能随细胞的营养供应而变化。将细胞内隔室隔开的膜对乙酰辅酶 A 是不可渗透的，并且隔室之间没有直接的运输发生。因此，没有肉碱供应时，乙醛酸支路是将乙酰辅酶 A 从细胞质或过氧化物酶体转移到线粒体的唯一可能途径。在这里，我们研究了在替代碳源下，acs1、acs2、cit2 和 mls1 的不同缺失突变体单独或组合的生理特征，并研究了各种突变如何改变碳分布。根据我们的结果，提出了酵母中细胞质和过氧化物酶体乙酰辅酶 A 代谢碳分布的详细模型。这对于进一步将酵母开发为乙酰辅酶 A 衍生产物生物合成的细胞工厂将是有用的。
