NAD+/NADH homeostasis affects metabolic adaptation to hypoxia and secondary metabolite production in filamentous fungi*
NAD+/NADH homeostasis affects metabolic adaptation to hypoxia and secondary metabolite production in filamentous fungi*
复制标题
DOI：
10.1080/09168451.2017.1422972
复制
发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Motoyuki Shimizu
中科院分区：
文献类型：
--
作者：
Motoyuki Shimizu
丝状真菌可用于生产发酵食品、有机酸、有益的次生代谢产物和各种酶。在这些过程中，这些真菌平衡细胞NAD+：NADH比率以适应环境氧化还原刺激。真菌细胞中的细胞NAD（H）状态是代谢途径（包括糖酵解、发酵以及有机酸、氨基酸和次级代谢产物的产生）变化的触发因素。在低氧条件下，高的NADH：NAD+比率导致各种脱氢酶的失活，并且与常氧条件相比，涉及NAD+的代谢流被下调。本文综述了缺氧条件下丝状真菌改变细胞内NADH：NAD+平衡的代谢机制。我们还讨论了细胞内的氧化还原平衡（NAD/NADH比）和生产的有益的次级代谢产物，产生抑制HDAC活性的sirtuin A通过nutrient水解酶A（NdxA）依赖的NAD+降解之间的关系。环境氧化还原刺激可诱导真菌代谢途径发生变化，如糖酵解、发酵以及有机酸、氨基酸和次生代谢产物的产生。
Abstract Filamentous fungi are used to produce fermented foods, organic acids, beneficial secondary metabolites and various enzymes. During such processes, these fungi balance cellular NAD+:NADH ratios to adapt to environmental redox stimuli. Cellular NAD(H) status in fungal cells is a trigger of changes in metabolic pathways including those of glycolysis, fermentation, and the production of organic acids, amino acids and secondary metabolites. Under hypoxic conditions, high NADH:NAD+ ratios lead to the inactivation of various dehydrogenases, and the metabolic flow involving NAD+ is down-regulated compared with normoxic conditions. This review provides an overview of the metabolic mechanisms of filamentous fungi under hypoxic conditions that alter the cellular NADH:NAD+ balance. We also discuss the relationship between the intracellular redox balance (NAD/NADH ratio) and the production of beneficial secondary metabolites that arise from repressing the HDAC activity of sirtuin A via Nudix hydrolase A (NdxA)-dependent NAD+ degradation. Fungal metabolic changes in the pathways such as glycolysis, fermentation, and the production of organic acids, amino acids and secondary metabolites are induced by environmental redox stimuli.