代谢工程改造枯草芽孢杆菌高效生产MK-7

Efficient Production of MK-7 by Metabolic Engineering in Bacillus subtilis

摘要:

七烯甲萘醌（MK-7）作为一种重要的K族维生素，在保健食品和医药制造领域具有良好的应用前景。为了得到一株高产MK-7菌株，作者以Bacillus subtilis 168为出发菌株，分别进行了代谢分支途径基因敲除、MK-7合成途径关键基因menA的突变体筛选优化、人工操纵子强化部分途径基因的表达来提升MK-7发酵产量。最终构建得到高产菌株MK7-13，发酵产MK-7达到（73.73±1.86） mg/L，与对照菌株相比提高了9.71倍，为后续微生物发酵法工业化生产MK-7奠定了基础。

Abstract:

Menaquinone-7 (MK-7) has a promising application prospect in the fields of health food and pharmaceutical manufacturing as an important vitamin of the K family. In this work, the yield of MK-7 fermentation was improved by using Bacillus subtilis 168 as the starting strain, knocking out the genes from metabolic branch pathways, screening and optimizing the mutant of speed-limited gene menA of the MK-7 synthesis pathway, and enhancing the expression of several MK-7 biosynthesis pathway genes through an artificial operon. Finally, a high-yield strain MK7-13 was developed with the yield of （73.73±1.86） mg/L, which was 9.71 times higher than that of the original strain. In summary, a high-yield MK-7 strain was successfully constructed by a combinatorial metabolic engineering strategy, which laid a foundation for the subsequent industrial production of MK-7 by microbial fermentation.