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Regulating triacylglycerol cycling for high-efficiency production of polyunsaturated fatty acids and derivatives
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Journal Article
Regulating triacylglycerol cycling for high-efficiency production of polyunsaturated fatty acids and derivatives
2025
Overview
Lipid degradation is generally considered an antagonistic pathway to lipid synthesis, so this pathway is often removed to improve lipid production. In this study, triacylglycerol (TAG) cycling formed by lipid degradation is found to be crucial for long-chain polyunsaturated fatty acid (PUFA) biosynthesis; this result contradicts the notion that lipid degradation is a useless process. Specifically, we demonstrate that TAG cycling promoting PUFA biosynthesis occurred in
Yarrowia lipolytica
and
Mortierella alpina
via the desaturase/elongase pathway but not in
Schizochytrium
sp. with the polyketide synthase (PKS) pathway. Exploiting the TAG cycling mechanism, a strategy of decoupling the TAG biosynthesis and degradation is developed. Using this strategy, the titers of C20:5, C22:5 and prostaglandin F2α (PGF2α) in
Y. lipolytica
are improved by 116.2%, 99.4% and 41.7%, respectively. Our findings highlight the potential of the TAG cycling for related biochemical synthesis in the construction of excellent oleaginous engineered strains.
The authors demonstrate the role and mechanism of triacylglycerol (TAG) cycling in polyunsaturated fatty acid biosynthesis and develop a strategy of decoupling the TAG biosynthesis and degradation to improve related biochemical synthesis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/77
/ Cycles
/ Fatty Acid Desaturases - genetics
/ Fatty Acid Desaturases - metabolism
/ Fatty Acid Elongases - metabolism
/ Fatty Acids, Unsaturated - biosynthesis
/ Fatty Acids, Unsaturated - metabolism
/ Fungal Proteins - metabolism
/ Humanities and Social Sciences
/ Lipids
/ Metabolic Engineering - methods
/ Polyketide Synthases - genetics
/ Polyketide Synthases - metabolism
/ Science
