Menaquinone biosynthesis in Lactococcus lactis: Recent advances and future prospects.

Menaquinone, also known as vitamin K2, has extensive nutritional and pharmaceutical applications, such as in bone health maintenance and cardiovascular protection. It consists of a naphthoquinone ring and a side chain with varying numbers of isoprenoid units; hence, it is abbreviated as MK-n, where n represents the number of isoprenoid units. Since long-chain MKs (n = 5-13), which are produced only by bacteria, exhibit longer half-lives and higher bioavailability than short-chain MKs, the microbial production of long-chain MKs has attracted great interest in the fields of food microbiology and synthetic biology. Lactococcus lactis, a key starter strain for dairy processing, is an excellent candidate as it produces MK-8, MK-9, and MK-10. In recent years, research on MK biosynthesis in L. lactis has gained increasing attention, and improvements in MK production have been achieved through physiological exploration, fermentation optimization, and metabolic engineering. This review summarizes the MK biosynthetic pathway, its physiological functions, and regulation of the MK profile as well as the production titer in L. lactis. Moreover, it discusses the high-yield schemes of MK in Escherichia coli and Bacillus subtilis to provide insights for developing L. lactis as an MK-producing cell factory.