Progress of metabolic engineering for the production of eicosapentaenoic acid

Jia, Yu-Lei; Song, Geng; Du, Fei; Xu, Ying‐Shuang; Wang, Ling‐Ru; Sun, Xiao‐Man; Wang, Qingzhuo; Li, Qi

doi:10.1080/07388551.2021.1971621

Cited by 9 publications

(7 citation statements)

References 166 publications

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“…Then, malonyl-CoA is condensed with another molecule of acetyl-CoA to form acyl-CoA, and the fatty acid (FA) chain is extended by two carbon atoms in each step. 16 In fungi, the elongation reaction catalyzed by fatty acid synthase (FAS) extends to 16 carbons, and the final product is palmitoyl-ACP. Palmitoyl ACP thioesterase releases palmitic acid (PA; 16:0) in the cytoplasm, which is then transferred to the endoplasmic reticulum for further conversion by fatty acid elongase 17 to form stearic acid (SA; 18:0).…”

Section: Biosynthetic Pathway Of Ara In Fungimentioning

confidence: 99%

“…In the desaturase/elongase pathway, acetyl-CoA is converted into malonyl-CoA by acetyl-CoA carboxylase (ACC). Then, malonyl-CoA is condensed with another molecule of acetyl-CoA to form acyl-CoA, and the fatty acid (FA) chain is extended by two carbon atoms in each step . In fungi, the elongation reaction catalyzed by fatty acid synthase (FAS) extends to 16 carbons, and the final product is palmitoyl-ACP.…”

Section: Biosynthetic Pathway Of Ara In Fungimentioning

confidence: 99%

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Recent Development of Advanced Biotechnology in the Oleaginous Fungi for Arachidonic Acid Production

Guo

Peng

et al. 2022

ACS Synth. Biol.

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Arachidonic acid is an essential ω-6 polyunsaturated fatty acid, which plays a significant role in cardiovascular health and neurological development, leading to its wide use in the food and pharmaceutical industries. Traditionally, ARA is obtained from deep-sea fish oil. However, this source is limited by season and is depleting the already threatened global fish stocks. With the rapid development of synthetic biology in recent years, oleaginous fungi have gradually attracted increasing attention as promising microbial sources for large-scale ARA production. Numerous advanced technologies including metabolic engineering, dynamic regulation of fermentation conditions, and multiomics analysis were successfully adapted to increase ARA synthesis. This review summarizes recent advances in the bioengineering of oleaginous fungi for ARA production. Finally, perspectives for future engineering approaches are proposed to further improve the titer yield and productivity of ARA.

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Section: Biosynthetic Pathway Of Ara In Fungimentioning

confidence: 99%

Section: Biosynthetic Pathway Of Ara In Fungimentioning

confidence: 99%

Recent Development of Advanced Biotechnology in the Oleaginous Fungi for Arachidonic Acid Production

Guo

Peng

et al. 2022

ACS Synth. Biol.

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“…According to reports, the market for omega-3 fatty acids will be expanding at the compound annual growth rate of 7.7% by 2027 [ 1 ]. Eicosapentaenoic acid (EPA, C20:5Δ 5, 8, 11, 14, 17 ), as an important long-chain ω- 3 polyunsaturated fatty acids (PUFAs), has been proven to have significant contributions to human health, thus occupying a place in the functional food and nutraceutical industry [ 2 ]. Currently, high-quality EPA is mainly extracted from deep-sea fish oil.…”

Section: Introductionmentioning

confidence: 99%

Identification of lipid synthesis genes in Schizochytrium sp. and their application in improving eicosapentaenoic acid synthesis in Yarrowia lipolytica

Jia,

Zhang,

et al. 2024

Biotechnol Biofuels

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Background Eicosapentaenoic acid (EPA) is widely used in the functional food and nutraceutical industries due to its important benefits to human health. Oleaginous microorganisms are considered a promising alternative resource for the production of EPA lipids. However, the storage of EPA in triglyceride (TG) becomes a key factor limiting its level. Results This study aimed to incorporate more EPA into TG storage through metabolic engineering. Firstly, key enzymes for TG synthesis, the diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase (GPAT) genes from Schizochytrium sp. HX-308 were expressed in Yarrowia lipolytica to enhance lipid and EPA accumulation. In addition, engineering the enzyme activity of DGATs through protein engineering was found to be effective in enhancing lipid synthesis by replacing the conserved motifs “HFS” in ScDGAT2A and “FFG” in ScDGAT2B with the motif “YFP”. Notably, combined with lipidomic analysis, the expression of ScDGAT2C and GPAT2 enhanced the storage of EPA in TG. Finally, the accumulation of lipid and EPA was further promoted by identifying and continuing to introduce the ScACC, ScACS, ScPDC, and ScG6PD genes from Schizochytrium sp., and the lipid and EPA titer of the final engineered strain reached 2.25 ± 0.03 g/L and 266.44 ± 5.74 mg/L, respectively, which increased by 174.39% (0.82 ± 0.02 g/L) and 282.27% (69.70 ± 0.80 mg/L) compared to the initial strain, respectively. Conclusion This study shows that the expression of lipid synthesis genes from Schizochytrium sp. in Y. lipolytica effectively improves the synthesis of lipids and EPA, which provided a promising target for EPA-enriched microbial oil production.

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“…The PKS gene cluster of Schizochytrium sp. was reported to consist of three open reading frames (ORFs): ORFA, ORFB, and ORFC, including 3-hydroxyacyl-ACP dehydratase (DH), acyltransferase (AT), 3-ketoacyl-ACP synthase (KS), malonyl-CoA: ACP acyltransferase (MAT), 3-ketoacyl-ACP reductase (KR), acyl carrier protein (ACP), and enoyl reductase (ER) domains. , Compared with the desaturase/elongase pathway, the PKS gene cluster requires less NADPH and produces fewer intermediate fatty acids. Therefore, in recent years, modifying the PKS cluster to improve PUFA production has become a hot topic of research. − …”

Section: Introductionmentioning

confidence: 99%

Function of the Polyketide Synthase Domains of Schizochytrium sp. on Fatty Acid Synthesis in Yarrowia lipolytica

Jia

Nong

et al. 2023

J. Agric. Food Chem.

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It is well known that polyunsaturated fatty acids (PUFAs) in Schizochytrium sp. are mainly synthesized via the polyketide synthase (PKS) pathway. However, the specific mechanism of PKS in fatty acid synthesis is still unclear. In this work, the functions of ORFA, ORFB, ORFC, and their individual functional domain genes on fatty acid synthesis were investigated through heterologous expression in Yarrowia lipolytica. The results showed that the expression of ORFA, ORFB, ORFC, and their individual functional domains all led to the increase of the very long-chain PUFA content (mainly eicosapentaenoic acid). Furthermore, the transcriptomic analysis showed that except for the 3-ketoacyl-ACP synthase (KS) domain of ORFB, the expression of an individual functional domain, including malonyl-CoA: ACP acyltransferase, 3-hydroxyacyl-ACP dehydratase (DH), 3-ketoacyl-ACP reductase, and KS domains of ORFA, acyltransferase domains of ORFB, and two DH domains of ORFC resulted in upregulation of the tricarboxylic acid cycle and pentose phosphate pathway, downregulation of the triacylglycerol biosynthesis, fatty acid synthesis pathway, and β-oxidation in Yarrowia lipolytica. These results provide a theoretical basis for revealing the function of PKS in fatty acid synthesis in Y. lipolytica and elucidate the possible mechanism for PUFA biosynthesis.

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Progress of metabolic engineering for the production of eicosapentaenoic acid

Cited by 9 publications

References 166 publications

Recent Development of Advanced Biotechnology in the Oleaginous Fungi for Arachidonic Acid Production

Recent Development of Advanced Biotechnology in the Oleaginous Fungi for Arachidonic Acid Production

Identification of lipid synthesis genes in Schizochytrium sp. and their application in improving eicosapentaenoic acid synthesis in Yarrowia lipolytica

Function of the Polyketide Synthase Domains of Schizochytrium sp. on Fatty Acid Synthesis in Yarrowia lipolytica

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