Lab of Brewing Microbiology and Applied Enzymology, Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan Universitygrid.258151.a, Wuxi, China.
The Center for Solid-state Fermentation Engineering of Anhui Province, Bozhou, China.
mSystems. 2022 Oct 26;7(5):e0053422. doi: 10.1128/msystems.00534-22. Epub 2022 Sep 8.
Caproate, an important medium-chain fatty acid, can only be synthesized by limited bacterial species by using ethanol, lactate, or certain saccharides. is a promising caproate producer due to its glucose and lactate utilization capabilities. However, the global cellular responses of this bacterium to different carbon sources were not well understood. Here, showed robust growth on glucose but more active caproate synthesis on lactate. Comparative transcriptome revealed that the genes involved in reverse β-oxidation for caproate synthesis and V-type ATPase-dependent ATP generation were upregulated under lactate condition, while several genes responsible for biomass synthesis were upregulated under glucose condition. Based on metabolic pathway reconstructions and bioenergetics analysis, the biomass accumulation on glucose condition may be supported by sufficient supplies of ATP and metabolite intermediates via glycolysis. In contrast, the ATP yield per glucose equivalent from lactate conversion into caproate was only 20% of that from glucose. Thus, the upregulation of the reverse β-oxidation genes may be essential for cell survival under lactate conditions. Furthermore, the remarkably decreased lactate utilization was observed after glucose acclimatization, indicating the negative modulation of lactate utilization by glucose metabolism. Based on the cotranscription of the lactate utilization repressor gene with sugar-specific PTS genes and the opposite expression patterns of and lactate utilization genes, a novel regulatory mechanism of glucose-repressed lactate utilization mediated via was proposed. The results of this study suggested the molecular mechanism underlying differential physiologic and metabolic characteristics of grown on glucose and lactate. is a unique and robust caproate-producing bacterium in the family Oscillospiraceae due to its lactate utilization capability, whereas its close relatives such as , Caproiciproducens galactitolivorans, and cannot utilize lactate but produce lactate as the main fermentation end product. Moreover, can also utilize several saccharides such as glucose and maltose. Although the metabolic versatility of the bacterium makes it to be a promising industrial caproate producer, the cellular responses of to different carbon sources were unknown. Here, the molecular mechanisms of biomass synthesis supported by glucose utilization and the cell survival supported by lactate utilization were revealed. A novel insight into the regulatory machinery in which glucose negatively regulates lactate utilization was proposed. This study provides a valuable basis to control and optimize caproate production, which will contribute to achieving a circular economy and environmental sustainability.
己酸是一种重要的中链脂肪酸，只能由有限的细菌种类通过使用乙醇、乳酸或某些糖来合成。由于其能够利用葡萄糖和乳酸，因此是一种很有前途的己酸生产菌。然而，该细菌对不同碳源的全局细胞反应尚不清楚。在这里，该细菌在葡萄糖上表现出强劲的生长，但在乳酸上表现出更活跃的己酸合成。比较转录组显示，参与己酸合成的反向β-氧化和 V 型 ATP 酶依赖的 ATP 生成的基因在乳酸条件下上调，而一些负责生物量合成的基因在葡萄糖条件下上调。基于代谢途径重建和生物能量学分析，在葡萄糖条件下生物量的积累可能得益于通过糖酵解提供足够的 ATP 和代谢物中间体。相比之下，从乳酸转化为己酸的每葡萄糖当量产生的 ATP 产量仅为葡萄糖的 20%。因此，反向β-氧化基因的上调对于在乳酸条件下细胞存活至关重要。此外，在葡萄糖适应后观察到乳酸利用显著减少，表明葡萄糖代谢对乳酸利用的负调控。基于乳酸利用抑制剂基因 与糖特异性 PTS 基因的共转录以及 和乳酸利用基因的相反表达模式，提出了一种通过 介导的葡萄糖抑制乳酸利用的新型调控机制。该研究结果表明了 在葡萄糖和乳酸上生长时的生理和代谢特征差异的分子机制。由于其利用乳酸的能力，是厚壁菌门 Oscillospiraceae 家族中一种独特而强大的己酸生产菌，而其近亲如 、Caproiciproducens galactitolivorans 和 不能利用乳酸，但作为主要发酵终产物产生乳酸。此外，还可以利用葡萄糖和麦芽糖等几种糖。尽管该细菌的代谢多功能性使其成为有前途的工业己酸生产菌，但对其不同碳源的细胞反应尚不清楚。在这里，揭示了葡萄糖利用支持的生物量合成的分子机制和乳酸利用支持的细胞存活的分子机制。提出了一种新的见解，即葡萄糖负调节乳酸利用的调控机制。该研究为控制和优化己酸生产提供了有价值的基础，这将有助于实现循环经济和环境可持续性。
