Riboflavin, an essential vitamin for animals, is used widely in the pharmaceutical industry and as a food and feed additive. The microbial synthesis of riboflavin requires a large amount of oxygen, which limits the industrial-scale production of the vitamin. In this study, a metabolic engineering strategy based on transcriptome analysis was identified as effective in increasing riboflavin production. First, transcriptional profiling revealed that hypoxia affects purine, and nitrogen metabolism. Next, the precursor supply pool was increased by purR knockout and tnrA and glnR knockdown to balance intracellular nitrogen metabolism. Finally, increased oxygen utilization was achieved by dynamically regulating vgb. Fed-batch fermentation of the engineered strain in a 5-liter bioreactor produced 10.71 g/l riboflavin, a 45.51% higher yield than that obtained with Bacillus subtilis RF1. The metabolic engineering strategy described herein is useful for alleviating the oxygen limitation of bacterial strains used for the industrial production of riboflavin and related products.

核黄素是动物必需的维生素，在制药工业中广泛用作食品和饲料添加剂。核黄素的微生物合成需要大量的氧气，这限制了维生素的工业规模生产。在这项研究中，基于转录组分析的代谢工程策略被认为可以有效地增加核黄素的产生。首先，转录谱分析表明缺氧会影响嘌呤和氮代谢。接下来，通过purR敲除以及tnrA和glnR敲低来增加前体供应池，以平衡细胞内氮的代谢。最后，通过动态调节vgb可以提高氧气利用率。在5升生物反应器中分批分批发酵工程菌株可产生10.71 g / l核黄素，比枯草芽孢杆菌RF1的产率高45.51％。本文所述的代谢工程策略可用于减轻用于工业生产核黄素和相关产品的细菌菌株的氧限制。