Production of Vitamin K by Wild-Type and Engineered Microorganisms

Abstract

Vitamin K is a fat-soluble vitamin that mainly exists as phylloquinone or menaquinone in nature. Vitamin K plays an important role in blood clotting and bone health in humans. For use as a nutraceutical, vitamin K is produced by natural extraction, chemical synthesis, and microbial fermentation. Natural extraction and chemical synthesis methods for vitamin K production have limitations, such as low yield of products and environmental concerns. Microbial fermentation is a more sustainable process for industrial production of natural vitamin K than two other methods. Recent advanced genetic technology facilitates industrial production of vitamin K by increasing the yield and productivity of microbial host strains. This review covers (i) general information about vitamin K and microbial host, (ii) current titers of vitamin K produced by wild-type microorganisms, and (iii) vitamin K production by engineered microorganisms, including the details of strain engineering strategies. Finally, current limitations and future directions for microbial production of vitamin K are also discussed.

First report on Vitamin B9 production including quantitative analysis of its vitamers in the yeast Scheffersomyces stipitis

“…The cone voltage was set to 60 V, and ramping collision energies ranged from 6 to 30 V to produce abundant ions before detection at the ToF. The mass spectrometer was calibrated with 0.5 M sodium formate and leucine–enkephalin (100 pg/μl) was used as LockMass (m/z 554.2615, 2 kV ionization voltage), which was infused simultaneously with the flow of column at 10 μl/min and acquired for 1 s each 10 s. The base peak chromatograms (BPI) were acquired at low [ 6 ] and high [ 30 ] energy from which the peaks identification was performed. Folate vitamers identity was confirmed by exploiting analytical standards as reference.…”

“…Biotechnology for Biofuels and Bioproducts Mastella et al Biotechnology for Biofuels and Bioproducts (2022) 15:98 with interesting examples including vitamins B 2 , B 12 , C, and K [3][4][5][6]. However, a biotechnological process for the large-scale production of vitamin B 9 (or folic acid, FA) has not been implemented yet, and the market still relies on its chemical production, which requires unsustainable, petroleum-based reagents [7].…”

“…Over the past few years, a large number of new nutraceuticals has been launched on the food and pharmaceutical market, among which vitamins represent an important category. In a scenario of environmental sustainability, biotechnological production of vitamins is starting to replace the chemical synthesis [ 2 ], with interesting examples including vitamins B 2 , B 12 , C, and K [ 3 – 6 ]. However, a biotechnological process for the large-scale production of vitamin B 9 (or folic acid, FA) has not been implemented yet, and the market still relies on its chemical production, which requires unsustainable, petroleum-based reagents [ 7 ].…”

Optimisation of the fermentation media to enhance the production of the bioactive isomer of vitamin menaquinone-7

“…Fermentation can also naturally enhance the nutrient profile and sensory characteristics of various products, thereby increasing their appeal to consumers [47,48]. Furthermore, microbial fermentation is a more sustainable process for the large-scale production of MK-7, and the use of natural production methods can help satisfy the market demand and sustainable development goals [49]. Many Gram-positive and Gram-negative bacterial strains can synthesise MK, which function as electron carriers in the respiratory chain [5,23,50].…”

“…Many Gram-positive and Gram-negative bacterial strains can synthesise MK, which function as electron carriers in the respiratory chain [5,23,50]. Both wild-type and engineered microorganisms have been used for MK-7 production via fermentation of which Bacillus strains, lactic acid bacteria, and various other types of microorganisms, such as Escherichia coli, Flavobacterium meningosepticum, Enterobacter agglomerans, Enterococcus faecium, and Serratia marcescens, tend to be the most common [49]. Nevertheless, members of the Bacillus species, such as Bacillus subtilis natto [51], Bacillus licheniformis [52], and Bacillus amylolyquifaciens [53], are the most notable [54].…”