Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone‑7
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 produc...
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| Veröffentlicht in: | ACS synthetic biology 2019-07, Vol.8 (7), p.1620-1630 |
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| creator | Ma, Yanwei McClure, Dale D Somerville, Mark V Proschogo, Nicholas W Dehghani, Fariba Kavanagh, John M Coleman, Nicholas V |
| description | 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. |
| doi_str_mv | 10.1021/acssynbio.9b00077 |
| format | Article |
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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. 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Biol</addtitle><description>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.</description><subject>Bacillus subtilis - metabolism</subject><subject>Bacterial Proteins - metabolism</subject><subject>Culture Media - metabolism</subject><subject>Fermentation - physiology</subject><subject>Metabolic Engineering - methods</subject><subject>Receptor, EphB6 - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Vitamin K 2 - analogs & derivatives</subject><subject>Vitamin K 2 - metabolism</subject><issn>2161-5063</issn><issn>2161-5063</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFOAjEQhhujEYM8gBfTF1hst9stHIWgkkDkoOdNuzuF4tJiuxvDzVfwFX0SS0DiydNMZv7vz8yP0A0lfUpSeifLEHZWGdcfKkKIEGfoKqU5TTjJ2fmfvoN6IayjhHDOOBtcog6j6X7DrtDbHBqpXG1KPLFLYwG8sUvsNG5WgOeTBV7IZvUhd9hYPJKlqes24NCqxtQmYO08ntrSgwxQ4ZFx8aQIhriKFnOw8r011ln4_vwS1-hCyzpA71i76PVh8jJ-SmbPj9Px_SyRjA2bhDHNSZUKQtJMMEoB0kqoLAeoQNEs54rwgS4HQwpaai04zVIQccb1kO1_7CJ68C29C8GDLrbebKTfFZQU--yKU3bFMbvI3B6Ybas2UJ2I36SiIDkIIlusXettfOEfwx_Du31W</recordid><startdate>20190719</startdate><enddate>20190719</enddate><creator>Ma, Yanwei</creator><creator>McClure, Dale D</creator><creator>Somerville, Mark V</creator><creator>Proschogo, Nicholas W</creator><creator>Dehghani, Fariba</creator><creator>Kavanagh, John M</creator><creator>Coleman, Nicholas V</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-3594-1754</orcidid><orcidid>https://orcid.org/0000-0002-7805-8101</orcidid></search><sort><creationdate>20190719</creationdate><title>Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone‑7</title><author>Ma, Yanwei ; McClure, Dale D ; Somerville, Mark V ; Proschogo, Nicholas W ; Dehghani, Fariba ; Kavanagh, John M ; Coleman, Nicholas V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a339t-33f50d2700247311ee2d7b46eedeb1465b058fc891efaff75142e70585f930553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Bacillus subtilis - metabolism</topic><topic>Bacterial Proteins - metabolism</topic><topic>Culture Media - metabolism</topic><topic>Fermentation - physiology</topic><topic>Metabolic Engineering - methods</topic><topic>Receptor, EphB6 - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>Vitamin K 2 - analogs & derivatives</topic><topic>Vitamin K 2 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Yanwei</creatorcontrib><creatorcontrib>McClure, Dale D</creatorcontrib><creatorcontrib>Somerville, Mark V</creatorcontrib><creatorcontrib>Proschogo, Nicholas W</creatorcontrib><creatorcontrib>Dehghani, Fariba</creatorcontrib><creatorcontrib>Kavanagh, John M</creatorcontrib><creatorcontrib>Coleman, Nicholas V</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>ACS synthetic biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Yanwei</au><au>McClure, Dale D</au><au>Somerville, Mark V</au><au>Proschogo, Nicholas W</au><au>Dehghani, Fariba</au><au>Kavanagh, John M</au><au>Coleman, Nicholas V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone‑7</atitle><jtitle>ACS synthetic biology</jtitle><addtitle>ACS Synth. Biol</addtitle><date>2019-07-19</date><risdate>2019</risdate><volume>8</volume><issue>7</issue><spage>1620</spage><epage>1630</epage><pages>1620-1630</pages><issn>2161-5063</issn><eissn>2161-5063</eissn><abstract>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. 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| subjects | Bacillus subtilis - metabolism Bacterial Proteins - metabolism Culture Media - metabolism Fermentation - physiology Metabolic Engineering - methods Receptor, EphB6 - metabolism Signal Transduction - physiology Vitamin K 2 - analogs & derivatives Vitamin K 2 - metabolism |
| title | Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone‑7 |
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