Engineering 3-Hydroxypropionic Acid Production from Glucose in <i>Yarrowia lipolytica</i> through Malonyl-CoA Pathway
3-Hydroxypropionic acid (3-HP) is an important intermediate compound in the chemical industry. Green and environmentally friendly microbial synthesis methods are becoming increasingly popular in a range of industries. Compared to other chassis cells, <i>Yarrowia lipolytica</i> possesses...
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MDPI AG
2023-05-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/5/573 |
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| author | Shiyu Liu Yao Sun Tianhui Wei Dianliang Gong Qi Wang Zhe Zhan Jinzhu Song |
| author_facet | Shiyu Liu Yao Sun Tianhui Wei Dianliang Gong Qi Wang Zhe Zhan Jinzhu Song |
| author_sort | Shiyu Liu |
| collection | DOAJ |
| description | 3-Hydroxypropionic acid (3-HP) is an important intermediate compound in the chemical industry. Green and environmentally friendly microbial synthesis methods are becoming increasingly popular in a range of industries. Compared to other chassis cells, <i>Yarrowia lipolytica</i> possesses advantages, such as high tolerance to organic acid and a sufficient precursor required to synthesize 3-HP. In this study, gene manipulations, including the overexpression of genes <i>MCR-N<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mi>C</mi><mi>a</mi></mrow></msub></semantics></math></inline-formula></i>, <i>MCR-C<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mi>C</mi><mi>a</mi></mrow></msub></semantics></math></inline-formula></i>, <i>GAPN<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mi>S</mi><mi>m</mi></mrow></msub></semantics></math></inline-formula></i>, <i>ACC1</i> and <i>ACS<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msubsup><mrow></mrow><mrow><mi>S</mi><mi>e</mi></mrow><mrow><mi>L</mi><mn>641</mn><mi>P</mi></mrow></msubsup></semantics></math></inline-formula></i> and knocking out bypass genes <i>MLS1</i> and <i>CIT2</i>, leading to the glyoxylate cycle, were performed to construct a recombinant strain. Based on this, the degradation pathway of 3-HP in <i>Y. lipolytica</i> was discovered, and relevant genes <i>MMSDH</i> and <i>HPDH</i> were knocked out. To our knowledge, this study is the first to produce 3-HP in <i>Y. lipolytica</i>. The yield of 3-HP in recombinant strain Po1f-NC-14 in shake flask fermentation reached 1.128 g·L<sup>−1</sup>, and the yield in fed-batch fermentation reached 16.23 g·L<sup>−1</sup>. These results are highly competitive compared to other yeast chassis cells. This study creates the foundation for the production of 3-HP in <i>Y. lipolytica</i> and also provides a reference for further research in the future. |
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| spelling | doaj.art-2b7100b7acdb4d63b89e345a9601eb582023-11-18T02:02:31ZengMDPI AGJournal of Fungi2309-608X2023-05-019557310.3390/jof9050573Engineering 3-Hydroxypropionic Acid Production from Glucose in <i>Yarrowia lipolytica</i> through Malonyl-CoA PathwayShiyu Liu0Yao Sun1Tianhui Wei2Dianliang Gong3Qi Wang4Zhe Zhan5Jinzhu Song6School of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, China3-Hydroxypropionic acid (3-HP) is an important intermediate compound in the chemical industry. Green and environmentally friendly microbial synthesis methods are becoming increasingly popular in a range of industries. Compared to other chassis cells, <i>Yarrowia lipolytica</i> possesses advantages, such as high tolerance to organic acid and a sufficient precursor required to synthesize 3-HP. In this study, gene manipulations, including the overexpression of genes <i>MCR-N<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mi>C</mi><mi>a</mi></mrow></msub></semantics></math></inline-formula></i>, <i>MCR-C<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mi>C</mi><mi>a</mi></mrow></msub></semantics></math></inline-formula></i>, <i>GAPN<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mi>S</mi><mi>m</mi></mrow></msub></semantics></math></inline-formula></i>, <i>ACC1</i> and <i>ACS<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msubsup><mrow></mrow><mrow><mi>S</mi><mi>e</mi></mrow><mrow><mi>L</mi><mn>641</mn><mi>P</mi></mrow></msubsup></semantics></math></inline-formula></i> and knocking out bypass genes <i>MLS1</i> and <i>CIT2</i>, leading to the glyoxylate cycle, were performed to construct a recombinant strain. Based on this, the degradation pathway of 3-HP in <i>Y. lipolytica</i> was discovered, and relevant genes <i>MMSDH</i> and <i>HPDH</i> were knocked out. To our knowledge, this study is the first to produce 3-HP in <i>Y. lipolytica</i>. The yield of 3-HP in recombinant strain Po1f-NC-14 in shake flask fermentation reached 1.128 g·L<sup>−1</sup>, and the yield in fed-batch fermentation reached 16.23 g·L<sup>−1</sup>. These results are highly competitive compared to other yeast chassis cells. This study creates the foundation for the production of 3-HP in <i>Y. lipolytica</i> and also provides a reference for further research in the future.https://www.mdpi.com/2309-608X/9/5/5733-hydroxypropionic acid<i>Yarrowia lipolytica</i>malonyl-CoAdegradation |
| spellingShingle | Shiyu Liu Yao Sun Tianhui Wei Dianliang Gong Qi Wang Zhe Zhan Jinzhu Song Engineering 3-Hydroxypropionic Acid Production from Glucose in <i>Yarrowia lipolytica</i> through Malonyl-CoA Pathway Journal of Fungi 3-hydroxypropionic acid <i>Yarrowia lipolytica</i> malonyl-CoA degradation |
| title | Engineering 3-Hydroxypropionic Acid Production from Glucose in <i>Yarrowia lipolytica</i> through Malonyl-CoA Pathway |
| title_full | Engineering 3-Hydroxypropionic Acid Production from Glucose in <i>Yarrowia lipolytica</i> through Malonyl-CoA Pathway |
| title_fullStr | Engineering 3-Hydroxypropionic Acid Production from Glucose in <i>Yarrowia lipolytica</i> through Malonyl-CoA Pathway |
| title_full_unstemmed | Engineering 3-Hydroxypropionic Acid Production from Glucose in <i>Yarrowia lipolytica</i> through Malonyl-CoA Pathway |
| title_short | Engineering 3-Hydroxypropionic Acid Production from Glucose in <i>Yarrowia lipolytica</i> through Malonyl-CoA Pathway |
| title_sort | engineering 3 hydroxypropionic acid production from glucose in i yarrowia lipolytica i through malonyl coa pathway |
| topic | 3-hydroxypropionic acid <i>Yarrowia lipolytica</i> malonyl-CoA degradation |
| url | https://www.mdpi.com/2309-608X/9/5/573 |
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