Li Yu-Xuan, Yue Sheng-Jie, Zheng Yi-Fan, Huang Peng, Nie Yan-Fang, Hao Xiang-Rui, Zhang Hong-Yan, Wang Wei, Hu Hong-Bo, Zhang Xue-Hong
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Shanghai Nong Le Biological Products Company Limited (NLBP), Shanghai 200240, China.
Biology (Basel). 2023 Sep 27;12(10):1292. doi: 10.3390/biology12101292.
Phenazine compounds are widely used in agricultural control and the medicine industry due to their high inhibitory activity against pathogens and antitumor activity. The green and sustainable method of synthesizing phenazine compounds through microbial fermentation often requires a complex culture medium containing tryptone and yeast extract, and its cost is relatively high, which greatly limits the large-scale industrial production of phenazine compounds by fermentation. The aim of this study was to develop a cost-effective minimal medium for the efficient synthesis of phenazine compounds by . Through testing the minimum medium commonly used by , an ME medium for with a high production of phenazine compounds was obtained. Then, the components of the ME medium and the other medium were compared and replaced to verify the beneficial promoting effect of Fe and NH on phenazine compounds. A cost-effective general defined medium (GDM) using glycerol as the sole carbon source was obtained by optimizing the composition of the ME medium. Using the GDM, the production of phenazine compounds by reached 1073.5 mg/L, which was 1.3 times that achieved using a complex medium, while the cost of the GDM was only 10% that of a complex medium (e.g., the KB medium). Finally, by engineering the glycerol metabolic pathway, the titer of phenazine-1-carboxylic acid reached the highest level achieved using a minimum medium so far. This work demonstrates how we systematically analyzed and optimized the composition of the medium and integrated a metabolic engineering method to obtain the most cost-effective fermentation strategy.
吩嗪化合物因其对病原体具有高抑制活性和抗肿瘤活性而广泛应用于农业防治和医药行业。通过微生物发酵合成吩嗪化合物的绿色可持续方法通常需要含有胰蛋白胨和酵母提取物的复杂培养基，且成本相对较高，这极大地限制了通过发酵大规模工业化生产吩嗪化合物。本研究的目的是开发一种具有成本效益的基本培养基，用于高效合成吩嗪化合物。通过测试常用的基本培养基，获得了一种用于吩嗪化合物高产的ME培养基。然后，对ME培养基和其他培养基的成分进行比较和替换，以验证铁和铵对吩嗪化合物的有益促进作用。通过优化ME培养基的组成，获得了一种以甘油为唯一碳源的具有成本效益的通用限定培养基（GDM）。使用GDM，吩嗪化合物的产量达到1073.5 mg/L，是使用复杂培养基时产量的1.3倍，而GDM的成本仅为复杂培养基（如KB培养基）的10%。最后，通过改造甘油代谢途径，吩嗪 - 1 - 羧酸的效价达到了目前使用基本培养基所达到的最高水平。这项工作展示了我们如何系统地分析和优化培养基的组成，并整合代谢工程方法以获得最具成本效益的发酵策略。
