A novel omega3-fatty acid desaturase involved in the biosynthesis of eicosapentaenoic acid

Pereira, Suzette L.; Huang, Y. S.; Bobik, E.; Kinney, Anthony J.; Stecca, Kevin L.; Packer, Jeremy C.L.; Mukerji, Pradip

doi:10.1042/bj20031319

Cited by 73 publications

(46 citation statements)

References 30 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…L41807), Synechosystis (GenBank accession no. 1653388), Arabidopsis thaliana (FAD3 gene), Saccharomyces kluyveri (22), Mortierella alpina (23), and Saprolegnia diclina (24).…”

Section: Discussionmentioning

confidence: 99%

Identification of bifunctional Δ12/ω3 fatty acid desaturases for improving the ratio of ω3 to ω6 fatty acids in microbes and plants

Damude

Zhang

Farrall

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

159

119

View full text Add to dashboard Cite

We report the identification of bifunctional ⌬12͞ 3 desaturases from Fusarium moniliforme, Fusarium graminearum, and Magnaporthe grisea. The bifunctional activity of these desaturases distinguishes them from all known ⌬12 or 3 fatty acid desaturases. The 3 desaturase activity of these enzymes also shows a broad 6 fatty acid substrate specificity by their ability to convert linoleic acid (LA), ␥-linolenic acid, di-homo-␥-linolenic acid, and arachidonic acid to the 3 fatty acids, ␣-linolenic acid (ALA), stearidonic acid, eicosatetraenoic acid, and eicosapentaenoic acid (EPA), respectively. Phylogenetic analysis suggests that 3 desaturases arose by independent gene duplication events from a ⌬12 desaturase ancestor. Expression of F. moniliforme ⌬12͞ 3 desaturase resulted in high ALA content in both Yarrowia lipolytica, an oleaginous yeast naturally deficient in 3 desaturation, and soybean. In soybean, seed-specific expression resulted in 70.9 weight percent of total fatty acid (%TFA) ALA in a transformed seed compared with 10.9%TFA in a null segregant seed and 53.2%TFA in the current best source of ALA, linseed oil. The ALA͞LA ratio in transformed seed was 22.3, a 110-and 7-fold improvement over the null segregant seed and linseed oil, respectively. Thus, these desaturases have potential for producing nutritionally desirable 3 longchain polyunsaturated fatty acids, such as EPA, with a significantly improved ratio of 3͞ 6 long-chain polyunsaturated fatty acids in both oilseeds and oleaginous microbes. polyunsaturated fatty acids ͉ Yarrowia ͉ soybean

show abstract

“…L41807), Synechosystis (GenBank accession no. 1653388), Arabidopsis thaliana (FAD3 gene), Saccharomyces kluyveri (22), Mortierella alpina (23), and Saprolegnia diclina (24).…”

Section: Discussionmentioning

confidence: 99%

Identification of bifunctional Δ12/ω3 fatty acid desaturases for improving the ratio of ω3 to ω6 fatty acids in microbes and plants

Damude

Zhang

Farrall

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

159

119

View full text Add to dashboard Cite

show abstract

“…This regulation of PUFA metabolic flux is partly due to the substrate specificity of the ∆6 Des Table 2, Sakuradani and Shimizu, 2003;Sakuradani et al, 2005;Zhu et al, 2002) which prefers n-6 fatty acid LA to n-3 ALA as substrate and its ω-3 Des must be repressed at physiological growth temperature (Shimizu et al, 1998). Although the ω-3 Des have been cloned and biochemically studied in a few microorganisms Table 5, (Gellerman and Schlenk, 1979;Pereira et al, 2004;Sakamoto et al, 1994;Wada and Murata, 1990), its expression level in oleaginous microorganisms has not been determined so far. However over-expression of ω-3 Des in Mt.…”

Section: Molecular Switch Of Microorganisms That Produce N-6 Fatty Acmentioning

confidence: 99%

Molecular Switch That Controls the Flux of Linoleic Acid Into N-6 or N-3 Polyunsaturated Fatty Acids in Microorganisms

Wang

Chen²,

Zhang

et al. 2014

American Journal of Biochemistry and Biotechnology

View full text Add to dashboard Cite

Polyunsaturated Fatty Acids (PUFA) of the n-6 and n-3 series play important roles in nutrition. Microorganisms are important sources of n-6 and n-3 fatty acids; however, most produce either n-6 or n-3 fatty acids as the major PUFAs and very few produce both. This differential production suggests that PUFAs metabolic pathway is strictly controlled in microorganisms. The major pathway of n-6/n-3 faty acids biosynthesis in lower eukaryotes is composed of ∆12 Desaturase (Des), ω3 Des (∆15, ∆17), ∆6 Des, ∆6 Elongase (Elo), ∆5 Des, ∆5 Elo and ∆4 Des, among which ∆6 Des and ∆15 (ω3) Des, located at the branch point of PUFAs metabolic pathways, are key regulators of the flux of linoleic acid (18:2 n-6) into either n-6 or n-3 fatty acid metabolic pathways. These latter two enzymes work together as a molecular switch that control the production of n-6/n-3 fatty acids. However the mechanism of the molecular switch is, so far, not clear. This review summarizes the recent advancement of the molecular base of the differentail production of n-6 or n-3 PUFAs in microorganisms.

show abstract

“…It impedes the conversion of the n6 into the n3 series, downstream in the pathway. Exceptions to this rule are the AA desaturase from Saprolegnia diclina (22), the o3 desaturase from Mortierella alpina (23) and FAT1 from Caenorhabditis elegans (24). Mammalian cells lack methyl-end desaturases, so they are absolutely dependent on the essential fatty acids linoleic acid (LA, 18:2D 9,12 ) and a-linolenic acid (ALA, 18:3D 9,12,15 ) taken from the diet as precursors for PUFA biosynthesis.…”

Section: Aerobic Pathwaymentioning

confidence: 99%

“…It has been used for years in the industry to produce AA-rich oils (9,10,30). All enzymes for synthesizing AA and EPA have been isolated and characterized, including the stearoyl CoA D9 desaturases (19), D12 and o3 methyl-end desaturases, D6 and D5 front-end desaturases and D6 elongase (10,13,22,30). Elongation appears to be the rate limiting step and overexpression of D6 elongase in M. alpina has been recently reported to improve the AA production (43).…”

Section: Pathways Found In Lower Eukaryotesmentioning

confidence: 99%

Biosynthesis of polyunsaturated fatty acids in lower eukaryotes

Uttaro

2006

IUBMB Life

View full text Add to dashboard Cite

SummaryPolyunsaturated fatty acids have important structural roles in cell membranes. They are also intermediates in the synthesis of biologically active molecules such as eicosanoids, which mediate fever, inflammation, blood pressure and neurotransmission. Arachidonic and docosahexaenoic acids are essential components of brain tissues and, through their involvement in the development of neural and retinal functions, important dietary nutrients for neonatal babies. Lower eukaryotes are particularly rich in C20-22 polyunsaturated fatty acids. Fungi and marine microalgae are currently used to produce nutraceutic oils. Other protists and algae are being studied because of the variability in their enzymes involved in polyunsaturated fatty acid biosynthesis. Such enzymes could be used as source for the production of transgenic organisms able to synthesize designed oils for human diet or, in the case of parasitic protozoa, they might be identified as putative chemotherapeutic targets. Polyunsaturated fatty acids can be synthesized by two different pathways: an anaerobic one, by using polyketide synthase related enzymes, and an aerobic one, which involves the action of elongases and oxygen dependent desaturases. Desaturases can be classified into three main types, depending on which of the consecutive steps of polyunsaturated fatty acid synthesis they are involved with. The enzymes may be specialized to act on: saturated substrates (type I); mono-and di-unsaturated fatty acids by introducing additional double bonds at the methyl-end site of the existing double bonds (type II); or the carboxy half ('front-end') of polyunsaturated ones (type III). Type III desaturases require the alternating action of elongases. A description of the enzymes that have been isolated and functionally characterized is provided, in order to highlight the different pathways found in lower eukaryotes.

show abstract

A novel omega3-fatty acid desaturase involved in the biosynthesis of eicosapentaenoic acid

Cited by 73 publications

References 30 publications

Identification of bifunctional Δ12/ω3 fatty acid desaturases for improving the ratio of ω3 to ω6 fatty acids in microbes and plants

Identification of bifunctional Δ12/ω3 fatty acid desaturases for improving the ratio of ω3 to ω6 fatty acids in microbes and plants

Molecular Switch That Controls the Flux of Linoleic Acid Into N-6 or N-3 Polyunsaturated Fatty Acids in Microorganisms

Biosynthesis of polyunsaturated fatty acids in lower eukaryotes

Contact Info

Product

Resources

About