Fatty acids are attractive biomolecules that have important applications in industry because of their high energy content and their use as precursors for other high-value chemicals. Bio-based production of fatty acids can enable sustainable substitution of petroleum-derived fuels and chemicals. In this paper, we used Saccharomyces cerevisiae BY4741 as a chassis cell to enhance the synthesis of free fatty acids (FFAs) through systematic metabolic engineering modifications. First, the synthesis of FFAs was enhanced by deleting the genes encoding acyl-CoA synthases FAA1, FAA4, and FAT1, and the FFAs of the yeast engineered strain reached 384.4 mg/L. Further, the β-oxidation pathway of the yeast cells was disrupted by knocking out POX1, FAA2, and PXA2, which further enhanced the extracellular FFAs to 394.9 mg/L. Subsequently, dephosphorylation of phosphatidic acid (PA) was reduced by knocking out the genes encoding phosphatidic acid phosphatases DPP1, LPP1, and PAH1, upregulating the ability of the obtained yeast engineered with multiple gene deletions (Δfaa1 Δfaa4 Δfat1 Δpox1 Δfaa2 Δpxa2 Δdpp1 Δlpp1 Δpah1) to produce 497.3 mg/L of extracellular free fatty acids, and 1332.2 mg/L of total fatty acids. The platform strains generated by combinatorial metabolic engineering provide a basis for the future development of lipid-related cell factories.
ZHU Manzhi
,
CHEN Xianzhong
,
SHEN Wei
,
YANG Haiquan
,
XIA Yuanyuan
. Metabolic engineering of Saccharomyces cerevisiae for efficient synthesis of free fatty acids[J]. Food and Fermentation Industries, 2024
, 50(2)
: 15
-22
.
DOI: 10.13995/j.cnki.11-1802/ts.035618
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