Journal Article10.1021/ACSSYNBIO.8B00258
Modular Pathway Engineering of Bacillus subtilis To Promote De Novo Biosynthesis of Menaquinone-7
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TL;DR: The final resulting strain MK3-MEP123-Gly2-Δ dhbB with simultaneous overexpression of menA, dxs, dxr, yacM-yacN, glpD and deletion ofdhbB enabled the yield of MK-7 to 69.5 ± 2.8 mg/L upon 144 h fermentation in a 2 L baffled flask.
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Abstract: Menaquinone-7 (MK-7), a valuable vitamin K2, plays an important role in the prevention of osteoporosis and cardiovascular calcification. We chose B. subtilis 168 as the chassis for the modular metabolic engineering design to promote the biosynthesis of MK-7. The biosynthetic pathway of MK-7 was categorized into four modules, namely, the MK-7 pathway (Module I), the shikimate (SA) pathway (Module II), the methylerythritol phosphate (MEP) pathway (Module III), and the glycerol metabolism pathway (Module IV). Overexpression of menA (Module I) resulted in 6.6 ± 0.1 mg/L of MK-7 after 120 h fermentation, which was 2.1-fold that of the starting strain BS168NU (3.1 ± 0.2 mg/L). Overexpression of aroA, aroD, and aroE (Module II) had a negative effect on the synthesis of MK-7. Simultaneous overexpression of dxs, dxr, yacM, and yacN (Module III) enabled the yield of MK-7 to 12.0 ± 0.1 mg/L. Moreover, overexpression of glpD (Module IV) resulted in an increase of the yield of MK-7 to 13.7 ± 0.2 mg/L. Furthermore, del...
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Bacillus subtilis: a universal cell factory for industry, agriculture, biomaterials and medicine.
TL;DR: This mini-review summarizes the basic genetic manipulation tools and expression systems for this bacterium, including traditional methods and novel engineering systems, and briefly introduces its applications in the production of chemicals and enzymes.
Vitamin K as a Diet Supplement with Impact in Human Health: Current Evidence in Age-Related Diseases.
TL;DR: The aim of this review is to update the reader regarding the specific contribution and effect of each K1 and K2 vitamers in human health, identify potential methods for its sustainable and cost-efficient production, and novel natural sources of vitamin K and formulations to improve absorption and bioavailability.
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Engineering a Bifunctional Phr60-Rap60-Spo0A Quorum-Sensing Molecular Switch for Dynamic Fine-Tuning of Menaquinone-7 Synthesis in Bacillus subtilis.
TL;DR: The bifunctional and modular Phr60-Rap60-Spo0A quorum sensing system has been successfully integrated with biocatalytic functions to achieve dynamic pathway regulation in B. subtilis 168 and may be extended for use in other microbes to fine-tune gene expression and improve metabolites production.
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Microbial production of vitamin K2: current status and future prospects.
TL;DR: The functions and applications of vitamin K2 are introduced first, after which the biosynthesis pathways and enzymes will be analyzed in-depth to highlight the bottlenecks facing the microbial vitamin K1 production on the industrial scale.
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Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone-7.
Yanwei Ma,Dale D. McClure,Mark V. Somerville,Nicholas Proschogo,Fariba Dehghani,John M. Kavanagh,Nicholas V. Coleman +6 more
TL;DR: This work highlights the usefulness of Bacillus subtilis for industrial production of high value compounds and reveals new bottlenecks in the pathway at IspG and IspH, which suggest avenues for further optimization.
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