Microbes have inherent capacities for utilizing various carbon sources, however they often exhibit sub-par fitness due to low metabolic efficiency. To test whether a bacterial strain can optimally utilize multiple carbon sources, was serially evolved in L-lactate and glycerol. This yielded two end-point strains that evolved first in L-lactate then in glycerol, and vice versa. The end-point strains displayed a universal growth advantage on single and a mixture of adaptive carbon sources, enabled by a concerted action of carbon source-specialists and generalist mutants. The combination of just four variants of , , , and , accounted for more than 80% of end-point strain fitness. In addition, machine learning analysis revealed a coordinated activity of transcriptional regulators imparting condition-specific regulation of gene expression. The effectiveness of the serial adaptive laboratory evolution (ALE) scheme in bioproduction applications was assessed under single and mixed-carbon culture conditions, in which serial ALE strain exhibited superior productivity of acetoin compared to ancestral strains. Together, systems-level analysis elucidated the molecular basis of serial evolution, which hold potential utility in bioproduction applications.

中文翻译：

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连续适应性实验室进化增强了大肠杆菌的混合碳代谢能力

微生物具有利用各种碳源的固有能力，但由于代谢效率低，它们常常表现出低于标准的适应性。为了测试细菌菌株是否能够最佳地利用多种碳源，在 L-乳酸和甘油中进行了连续进化。这产生了两个终点菌株，它们首先在 L-乳酸中进化，然后在甘油中进化，反之亦然。通过碳源专家和通才突变体的协调行动，终点菌株在单一和混合适应性碳源上表现出普遍的生长优势。 、 、 和 的四种变体的组合就占了终点应变适应性的 80% 以上。此外，机器学习分析揭示了转录调节因子的协调活动，可对基因表达进行条件特异性调节。在单一和混合碳培养条件下评估了系列适应性实验室进化（ALE）方案在生物生产应用中的有效性，其中系列 ALE 菌株与祖先菌株相比表现出更高的乙偶姻生产率。总之，系统级分析阐明了连续进化的分子基础，这在生物生产应用中具有潜在的实用性。