Department of Life Sciences, Faculty of Life and Environmental Sciences, Shimane University, 1060 Nishikawatsu, Matsue, 690-8504, Japan.
Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University, 1060 Nishikawatsu, Matsue, 690-8504, Japan.
Appl Microbiol Biotechnol. 2019 Jun;103(12):4899-4915. doi: 10.1007/s00253-019-09843-7. Epub 2019 Apr 27.
Coenzyme Q (CoQ) is an essential component of the electron transport system that produces ATP in nearly all living cells. CoQ is a popular commercial food supplement around the world, and demand for efficient production of this molecule has increased in recent years. In this study, we explored CoQ production in the fission yeast Schizosaccharomyces pombe. We found that CoQ level was higher in stationary phase than in log phase, and that it increased when the cells were grown in a low concentration of glucose, in maltose, or in glycerol/ethanol medium. Because glucose signaling is mediated by cAMP, we evaluated the involvement of this pathway in CoQ biosynthesis. Loss of Pka1, the catalytic subunit of cAMP-dependent protein kinase, increased production of CoQ, whereas loss of the regulatory subunit Cgs1 decreased production. Manipulation of other components of the cAMP-signaling pathway affected CoQ production in a consistent manner. We also found that glycerol metabolism was controlled by the cAMP/PKA pathway. CoQ production by the S. pombe ∆pka1 reached 0.98 mg/g dry cell weight in medium containing a non-fermentable carbon source [2% glycerol (w/v) and 1% ethanol (w/v) supplemented with 0.5% casamino acids (w/v)], twofold higher than the production in wild-type cells under normal growth conditions. These findings demonstrate that carbon source, growth phase, and the cAMP-signaling pathway are important factors in CoQ production in S. pombe.
辅酶 Q(CoQ)是电子传递系统的必需组成部分,几乎在所有活细胞中都能产生 ATP。CoQ 是一种在全球范围内流行的商业食品补充剂,近年来对这种分子的高效生产的需求有所增加。在这项研究中,我们探索了裂殖酵母 Schizosaccharomyces pombe 中的 CoQ 生产。我们发现,CoQ 水平在静止期高于对数期,并且当细胞在低浓度葡萄糖、麦芽糖或甘油/乙醇培养基中生长时,CoQ 水平会增加。由于葡萄糖信号由 cAMP 介导,我们评估了该途径在 CoQ 生物合成中的参与。cAMP 依赖性蛋白激酶催化亚基 Pka1 的缺失增加了 CoQ 的产生,而调节亚基 Cgs1 的缺失则降低了 CoQ 的产生。cAMP 信号通路的其他成分的操纵以一致的方式影响 CoQ 的产生。我们还发现甘油代谢受 cAMP/PKA 途径控制。含有不可发酵碳源[2%甘油(w/v)和 1%乙醇(w/v),补充 0.5% 水解酪蛋白(w/v)]的培养基中,S. pombe ∆pka1 的 CoQ 产量达到 0.98mg/g 干细胞重量,比正常生长条件下野生型细胞的产量高两倍。这些发现表明碳源、生长阶段和 cAMP 信号通路是 S. pombe 中 CoQ 生产的重要因素。