Engineering 3-Hydroxypropionic Acid Production from Glucose in Yarrowia lipolytica 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, Yarrowia lipolytica 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 MCR-N-Ca, MCR-C-Ca, GAPN(Sm), ACC1 and ACS(Se)(L641P) and knocking out bypass genes MLS1 and CIT2, leading to the glyoxylate cycle, were performed to construct a recombinant strain. Based on this, the degradation pathway of 3-HP in Y. lipolytica was discovered, and relevant genes MMSDH and HPDH were knocked out. To our knowledge, this study is the first to produce 3-HP in Y. lipolytica. The yield of 3-HP in recombinant strain Po1f-NC-14 in shake flask fermentation reached 1.128 g.L-1, and the yield in fed-batch fermentation reached 16.23 g.L-1. These results are highly competitive compared to other yeast chassis cells. This study creates the foundation for the production of 3-HP in Y. lipolytica and also provides a reference for further research in the future.

Automated summary

This study constructed a recombinant strain and discovered the degradation pathway of 3-HP in Y. lipolytica, successfully producing 3-HP in this strain. The yield of 3-HP reached 1.128 g/L in shake flask fermentation and 16.23 g/L in fed-batch fermentation, which are highly competitive compared to other yeast chassis cells. This study lays the foundation for the production of 3-HP in Y. lipolytica and provides a reference for future research.