Bacillus methanolicus MGA3 is a thermotolerant and relatively fast-growing methylotroph able to secrete large quantities of glutamate and lysine. These natural characteristics make B. methanolicus a good candidate to become a new industrial chassis organism, especially in a methanol-based economy. Intriguingly, the only substrates known to support B. methanolicus growth as sole sources of carbon and energy are methanol, mannitol, and, to a lesser extent, glucose and arabitol. Because fluxomics provides the most direct readout of the cellular phenotype, we hypothesized that comparing methylotrophic and nonmethylotrophic metabolic states at the flux level would yield new insights into MGA3 metabolism. In this study, we designed and performed a ¹³C metabolic flux analysis (¹³C-MFA) of the facultative methylotroph B. methanolicus MGA3 growing on methanol, mannitol, and arabitol to compare the associated metabolic states. On methanol, results showed a greater flux in the ribulose monophosphate (RuMP) pathway than in the tricarboxylic acid (TCA) cycle, thus validating previous findings on the methylotrophy of B. methanolicus. New insights related to the utilization of cyclic RuMP versus linear dissimilation pathways and between the RuMP variants were generated. Importantly, we demonstrated that the linear detoxification pathways and the malic enzyme shared with the pentose phosphate pathway have an important role in cofactor regeneration. Finally, we identified, for the first time, the metabolic pathway used to assimilate arabitol. Overall, those data provide a better understanding of this strain under various environmental conditions.

中文翻译：

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绘制兼性甲基营养型甲醇芽孢杆菌的代谢图谱。

甲醇芽孢杆菌MGA3 是一种耐热且生长相对快速的甲基营养菌，能够分泌大量的谷氨酸盐和赖氨酸。这些自然特性使甲醇 B.成为新的工业底盘生物的良好候选者，特别是在以甲醇为基础的经济中。有趣的是，已知支持甲醇双歧杆菌生长的唯一底物是甲醇、甘露醇，以及在较小程度上的葡萄糖和阿拉伯糖醇。由于通量组学提供了最直接的细胞表型读数，我们假设在通量水平上比较甲基营养和非甲基营养代谢状态将产生对 MGA3 代谢的新见解。在本研究中，我们设计并执行了¹³Ç代谢通量分析（¹³兼甲基营养的C-MFA）B. methanolicus MGA3甲醇，甘露糖醇，和阿拉伯糖醇生长比较相关的代谢状态。在甲醇中，结果显示单磷酸核酮糖 (RuMP) 途径中的通量大于三羧酸 (TCA) 循环中的通量，从而验证了先前关于甲醇双歧杆菌甲基营养的发现. 产生了与循环 RuMP 与线性异化途径的利用以及 RuMP 变体之间的利用相关的新见解。重要的是，我们证明了线性解毒途径和与磷酸戊糖途径共享的苹果酸酶在辅因子再生中具有重要作用。最后，我们首次确定了用于同化阿拉伯糖醇的代谢途径。总体而言，这些数据可以更好地了解这种菌株在各种环境条件下的情况。