Metabolic Engineering Strategy for Bacillus subtilis Producing MK-7.
Shiying Wu, Xiuwen Sun, Tingwen Fan, Fei Lin, Yuan Chi, Huaiyi Yang, Chunhui Zhao
Abstract
Open AccessMenaquinone-7 (MK-7) is an important bioactive form of vitamin K2 that inhibits vascular calcification, maintains systemic calcium homeostasis, demonstrates high bioavailability, and possesses an extended plasma half-life. Bacillus subtilis naturally possesses the complete biosynthetic pathway for MK-7, benefits from a well-characterized genetic background and advanced genome-editing tools, and is regarded as a safe and efficient microbial chassis for industrial MK-7 fermentation. This review summarizes recent advances in the metabolic engineering of Bacillus subtilis for high-level MK-7 production, highlights pathway analyses, and discusses engineering strategies targeting four key modules: substrate utilization, secretion, spore/biofilm formation, and oxidative-stress defense.