Impact of activation of neotrehalosadiamine/kanosamine biosynthetic pathway on the metabolism of .

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.