Abstract
A strain MMH-56 of Bacillus subtilis subsp. natto with a high productivity of menaquinone-7 (MK-7) was obtained by physico-chemical mutagenesis. Transcriptomic analysis demonstrated that the efficient synthesis of MK-7 in strain MMH-56 was correlated to the enhanced central carbon metabolic and shikimate pathways, along with the activated fatty acid metabolic pathway in the MK-7 synthesis process. Especially, the expressions of menA, menB, menD, and menE in the shikimate pathway were upregulated; while, AroA, AroC, AroH, AroK, and TyrA were down-regulated, compared to the wild-type. Such ingenious regulations released the feedback-inhibition of MK-7 synthesis from aromatic amino acids, and promoted the biosynthesis of MK-7. Additionally, fermentation medium for MK-7 production were further optimized by response surface methodology. A final concentration of 161.74 mg/L MK-7 was acquired, which was 62.93-fold higher than the wild-type. Such productivity was sufficient for the industrial production of MK-7.
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