Metabolomic Analysis of Cooperative Adaptation between Co-Cultured Bacillus cereus and Ketogulonicigenium vulgare

The cooperative adaptation of subcultivated Bacillus cereus and Ketogulonicigenium vulgare significantly increased the productivity of 2-keto-L-gulonic acid, the precursor of vitamin C. The mechanism of cooperative adaptation of the serial subcultivated B. cereus and K. vulgare was investigated in this study by culturing the two strains orthogonally on agar plates. It was found that the swarming distance of B. cereus along the trace of K. vulgare on the plate decreased after 150 days' subcultivation. Metabolomic analysis on these co-cultured B. cereus and K. vulgare strains showed that their cooperative adaptation was accomplished by three key events: (i) the ability of nutrients (e.g., amino acids and purines) searching and intaking, and proteins biosynthesis is increased in the evolved B. cereus; (ii) the capability of protein degradation and amino acids transportation is enhanced in evolved K. vulgare; (iii) the evolved B. cereus was found to provide more nutrients (mostly amino acids and purines) to K. vulgare, thus strengthening the oxidation and energy generation of K. vulgare. Our results provided novel insights into the systems-level understanding of the cooperative adaptation between strains in synergistic consortium.经连续传代培养的蜡样芽孢杆菌（Bacillus cereus）与普通酮古龙酸杆菌（Ketogulonicigenium vulgare）的协同适应性进化，显著提升了维生素C前体2-酮基-L-古龙酸（2-keto-L-gulonic acid）的合成产率。本研究通过将两株菌在琼脂平板上进行正交培养，探究了连续传代的蜡样芽孢杆菌与普通酮古龙酸杆菌的协同适应机制。研究发现，经过150天传代培养后，蜡样芽孢杆菌在普通酮古龙酸杆菌菌落迹线上的群游距离有所缩短。对上述共培养菌株的代谢组学（metabolomics）分析表明，二者的协同适应通过三项关键事件得以实现：(i) 进化后的蜡样芽孢杆菌对氨基酸、嘌呤等营养物质的搜寻与摄取能力，以及蛋白质生物合成功能均得到增强；(ii) 进化后的普通酮古龙酸杆菌的蛋白质降解与氨基酸转运能力得以提升；(iii) 进化后的蜡样芽孢杆菌可为普通酮古龙酸杆菌提供更多营养物质（主要为氨基酸与嘌呤），从而强化后者的氧化反应与能量生成过程。本研究结果为从系统层面理解协同菌群中菌株间的协同适应机制提供了全新视角。