Saito Natsumi, Nguyen Huong Minh, Inaoka Takashi
National Institute of Technology, Tsuruoka College, 104 Sawada, Inooka, Tsuruoka, Yamagata 997-8511, Japan.
Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Ha Noi, Viet Nam.
J Bacteriol. 2021 May 1;203(9). doi: 10.1128/JB.00603-20. Epub 2021 Feb 22.
The pentose phosphate (PP) pathway is one of the major sources of cellular NADPH. A mutant that lacks glucose-6-phosphate dehydrogenase (the enzyme that catalyzes the first step of the PP pathway) showed inoculum-dose-dependent growth. This growth defect was suppressed by disruption, which causes the upregulation of an autoinducer neotrehalosadiamine (NTD)/kanosamine biosynthetic pathway. A metabolome analysis showed that the stimulation of NTD/kanosamine biosynthesis caused significant accumulation of TCA cycle intermediates and NADPH. Because the major malic enzyme YtsJ concomitantly generates NADPH through malate-to-pyruvate conversion, NTD/kanosamine biosynthesis can result in an increase in the intracellular NADPH pool via the accumulation of malate. In fact, a mutant grew in malate-supplemented medium. Artificial induction of in the mutant caused a reduction in the intracellular NADPH pool. Moreover, the correlation between the expression level of the NTD/kanosamine biosynthesis operon and the intracellular NADPH pool was confirmed. Our results suggest that NTD/kanosamine has the potential to modulate the carbon-energy metabolism through an autoinduction mechanism.Autoinducers enable bacteria to sense cell density and to coordinate collective behavior. NTD/kanosamine is an autoinducer produced by and several close relatives, although its physiological function remains unknown. The most important finding of this study was the significance of NTD/kanosamine biosynthesis in the modulation of the central carbon metabolism in We showed that NTD/kanosamine biosynthesis caused an increase in the NADPH pool via the accumulation of TCA cycle intermediates. These results suggest a possible role for NTD/kanosamine in the carbon-energy metabolism. As species are widely used for the industrial production of various useful enzymes and compounds, the NTD/kanosamine biosynthetic pathway might be utilized to control metabolic pathways in these industrial strains.
磷酸戊糖（PP）途径是细胞内NADPH的主要来源之一。一个缺乏葡萄糖-6-磷酸脱氢酶（催化PP途径第一步的酶）的突变体表现出接种剂量依赖性生长。这种生长缺陷通过破坏得以抑制，破坏导致自诱导剂新海藻二胺（NTD）/甘露糖胺生物合成途径上调。代谢组分析表明，NTD/甘露糖胺生物合成的刺激导致三羧酸循环中间体和NADPH显著积累。由于主要的苹果酸酶YtsJ通过苹果酸向丙酮酸的转化同时产生NADPH，NTD/甘露糖胺生物合成可通过苹果酸的积累导致细胞内NADPH池增加。事实上，一个突变体在补充苹果酸的培养基中生长。在突变体中人工诱导导致细胞内NADPH池减少。此外，还证实了NTD/甘露糖胺生物合成操纵子的表达水平与细胞内NADPH池之间的相关性。我们的结果表明，NTD/甘露糖胺有可能通过自诱导机制调节碳能量代谢。自诱导剂使细菌能够感知细胞密度并协调集体行为。NTD/甘露糖胺是由[具体细菌名称]及其几个近亲产生的自诱导剂，尽管其生理功能尚不清楚。这项研究最重要的发现是NTD/甘露糖胺生物合成在调节[具体细菌名称]中心碳代谢中的重要性。我们表明，NTD/甘露糖胺生物合成通过三羧酸循环中间体的积累导致NADPH池增加。这些结果表明NTD/甘露糖胺在碳能量代谢中可能发挥作用。由于[具体细菌名称]物种被广泛用于各种有用酶和化合物的工业生产，NTD/甘露糖胺生物合成途径可能被用于控制这些工业菌株中的代谢途径。
