Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone-7.,ACS Synthetic Biology

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Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone-7.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2019-06-28 , DOI: 10.1021/acssynbio.9b00077
Yanwei Ma ₁ , Dale D McClure ₁ , Mark V Somerville ₂ , Nicholas W Proschogo ₃ , Fariba Dehghani ₁ , John M Kavanagh ₁ , Nicholas V Coleman ₂

Affiliation

Vitamin K is essential for blood coagulation and plays important roles in bone and cardiovascular health. Menaquinone-7 (MK-7) is one form of vitamin K that is especially useful due to its long half-life in the circulation. MK-7 is difficult to make via organic synthesis, and is thus commonly produced by fermentation. This study aimed to genetically modify Bacillus subtilis cultures to increase their MK-7 yield and reduce production costs. We constructed 12 different strains of B. subtilis 168 by overexpressing different combinations of the rate-limiting enzymes Dxs, Dxr, Idi, and MenA. We observed an 11-fold enhancement of production in the best-performing strain, resulting in 50 mg/L MK-7. Metabolite analysis revealed new bottlenecks in the pathway at IspG and IspH, which suggest avenues for further optimization. This work highlights the usefulness of Bacillus subtilis for industrial production of high value compounds.

中文翻译：

枯草芽孢杆菌中 MEP 途径的代谢工程用于增加 Menaquinone-7 的生物合成。

维生素 K 对血液凝固至关重要，并在骨骼和心血管健康中发挥重要作用。Menaquinone-7 (MK-7) 是维生素 K 的一种形式，由于其在循环中的长半衰期而特别有用。MK-7难以通过有机合成制备，因此通常通过发酵生产。本研究旨在对枯草芽孢杆菌培养物进行基因改造，以提高其 MK-7 产量并降低生产成本。我们通过过表达限速酶 Dxs、Dxr、Idi 和 MenA 的不同组合构建了 12 种不同的枯草芽孢杆菌 168 菌株。我们观察到表现最好的菌株的产量提高了 11 倍，产生了 50 mg/L MK-7。代谢物分析揭示了 IspG 和 IspH 通路中的新瓶颈，这为进一步优化提供了途径。

更新日期：2019-06-19

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