Taking the industrial pleuromutilin fermentation with strain Pleurotus mutilus as an example, the variations of small molecule metabolomes in different industrial fermentation processes were analyzed. The small molecule metabolomes in different processes were measured by gas chromatography coupled to time-of-flight mass spectrometry. Principal component analysis (PCA) was performed on the metabolome of P. Mutilus. According to the score plot and loading plot obtained by PCA, the similarities and differences of metabolism of P. Mutilus in two processes were extracted and classified. The analysis on characteristic metabolites indicated significant effects of different processes on cell viabilities. The higher level of TCA cycle intermediates and amino acids during the seed culture stage in the process two indicated higher carbon and nitrogen metabolism in P. Mutilus before the inoculation. In addition, the analysis of the variations of metabolites during the two different fermentation processes suggested that nutrition utilization efficiency of P. Mutilus in process two was higher than that in process one. This study indicates that metabolome analysis could be a new approach to evaluating the industrial bioprocess and is helpful in providing the feasible regulation scheme to improve the fermentation process.%引言rn为了提高抗生素生产水平,前人从反应器设计[1]、发酵条件优化[2]以及菌株改造[3]等方面进行了较深入的研究并取得了明显研究成效.然而抗生素发酵是一个受多种因素影响的复杂过程,特别是发酵环境对抗生素发酵单位的影响十分显著[4],其中发酵环境涉及物理、化学、生物等多种因素的影响,因此常规的发酵过程调控是一个较为烦琐的多因素优化工作.对这种复杂的生物反应体系,系统生物学可从整体水平对发酵环境与培养菌株之间的相互作用加以研究.其中,利用代谢组学(系统生物学的一个分支)不仅可以揭示菌株本身的代谢特性,更重要的是可以提供菌株的代谢特性与发酵环境变化相互关联的生物工程信息[5-6].本文作者曾利用代谢组学手段,对工业乙醇的连续发酵与间歇发酵过程[7]、环境中复合抑制剂对发酵过程的影响进行了研究[8],表明该方法具有较广阔的应用前景.本文以一种常用的兽用抗生素泰妙菌素的前体——截短侧耳素的生产过程为例,对其工业发酵过程中的生产菌株Pleurotus mutilus进行代谢组学分析,以期为抗生素工业发酵过程的优化提供一种新的思路.
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