Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone-7
| Autor: | John M. Kavanagh, Mark V. Somerville, Yanwei Ma, Nicholas Proschogo, Nicholas V. Coleman, Fariba Dehghani, Dale D. McClure |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
chemistry.chemical_classification 0303 health sciences Strain (chemistry) biology Biomedical Engineering Biofilm General Medicine Bacillus subtilis Vitamin k biology.organism_classification 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Metabolic engineering 03 medical and health sciences chemistry.chemical_compound Enzyme Biochemistry Biosynthesis chemistry 010608 biotechnology Fermentation 030304 developmental biology |
| Zdroj: | ACS Synthetic Biology. 8:1620-1630 |
| ISSN: | 2161-5063 |
| DOI: | 10.1021/acssynbio.9b00077 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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