scholarly journals Identification of a Caenorhabditis elegans Δ6-fatty-acid-desaturase by heterologous expression in Saccharomyces cerevisiae

1998 ◽  
Vol 330 (2) ◽  
pp. 611-614 ◽  
Author(s):  
A. Johnathan NAPIER ◽  
J. Sandra HEY ◽  
J. Dominic LACEY ◽  
R. Peter SHEWRY
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Fatty Acid ◽  
Caenorhabditis Elegans ◽  
Expressed Sequence Tag ◽  
Cytochrome B5 ◽  
Fatty Acid Desaturase ◽  
Higher Plant ◽  
Yeast Saccharomyces Cerevisiae ◽  
C Elegans ◽  
Δ6 Desaturase

We identified a cDNA expressed sequence tag from an animal (the nematode worm Caenorhabditis elegans) that showed weak similarity to a higher-plant microsomal Δ6-desaturase. A full-length cDNA clone was isolated and expressed in the yeast Saccharomyces cerevisiae. This demonstrated that the protein encoded by the C. elegans cDNA was that of a fatty acid Δ6-desaturase, as determined by the accumulation of γ-linolenic acid. The C. elegans Δ6-desaturase contained an N-terminalcytochrome b5 domain, indicating that it had a similar structure to that of the higher-plant Δ6-desaturase. The C. elegans Δ6-desaturase mapped to cosmid W08D2, a region of chromosome III. This is the first example of a Δ6-desaturase isolated from an animal and also the first example of an animal desaturase containing a cytochrome b5 domain.

scholarly journals Juniperonic Acid Biosynthesis is Essential in Caenorhabditis elegans Lacking Δ6 Desaturase (fat-3) and Generates New ω-3 Endocannabinoids

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2127
Author(s):  
Sujay Guha ◽  
Serafina Calarco ◽  
M. Salomé Gachet ◽  
Jürg Gertsch
Keyword(s):  
Fatty Acid ◽  
Caenorhabditis Elegans ◽  
Polyunsaturated Fatty Acid ◽  
Loss Of Function ◽  
Compensatory Mechanisms ◽  
C Elegans ◽  
Juniperonic Acid ◽  
Endocannabinoid Receptor ◽  
G Protein Coupled ◽  
Δ6 Desaturase

In eukaryotes, the C20:4 polyunsaturated fatty acid arachidonic acid (AA) plays important roles as a phospholipid component, signaling molecule and precursor of the endocannabinoid-prostanoid axis. Accordingly, the absence of AA causes detrimental effects. Here, compensatory mechanisms involved in AA deficiency in Caenorhabditis elegans were investigated. We show that the ω-3 C20:4 polyunsaturated fatty acid juniperonic acid (JuA) is generated in the C. elegans fat-3(wa22) mutant, which lacks Δ6 desaturase activity and cannot generate AA and ω-3 AA. JuA partially rescued the loss of function of AA in growth and development. Additionally, we observed that supplementation of AA and ω-3 AA modulates lifespan of fat-3(wa22) mutants. We described a feasible biosynthetic pathway that leads to the generation of JuA from α-linoleic acid (ALA) via elongases ELO-1/2 and Δ5 desaturase which is rate-limiting. Employing liquid chromatography mass spectrometry (LC-MS/MS), we identified endocannabinoid-like ethanolamine and glycerol derivatives of JuA and ω-3 AA. Like classical endocannabinoids, these lipids exhibited binding interactions with NPR-32, a G protein coupled receptor (GPCR) shown to act as endocannabinoid receptor in C. elegans. Our study suggests that the eicosatetraenoic acids AA, ω-3 AA and JuA share similar biological functions. This biosynthetic plasticity of eicosatetraenoic acids observed in C. elegans uncovers a possible biological role of JuA and associated ω-3 endocannabinoids in Δ6 desaturase deficiencies, highlighting the importance of ALA.

scholarly journals Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Hildegard I. D. Mack ◽  
Jennifer Kremer ◽  
Eva Albertini ◽  
Elisabeth K. M. Mack ◽  
Pidder Jansen-Dürr
Keyword(s):  
Fatty Acid ◽  
Caenorhabditis Elegans ◽  
Insulin Receptor ◽  
Genetic Background ◽  
Expression Patterns ◽  
Fatty Acid Desaturase ◽  
Pathogen Resistance ◽  
Global Changes ◽  
C Elegans ◽  
Receptor Mutant

Abstract Background In the nematode Caenorhabditis elegans, longevity in response to germline ablation, but not in response to reduced insulin/IGF1-like signaling, is strongly dependent on the conserved protein kinase minibrain-related kinase 1 (MBK-1). In humans, the MBK-1 ortholog DYRK1A is associated with a variety of disorders, most prominently with neurological defects observed in Down syndrome. To better understand mbk-1’s physiological roles and their dependence on genetic background, we analyzed the influence of mbk-1 loss on the transcriptomes of wildtype and long-lived, germline-deficient or insulin-receptor defective, C. elegans strains by RNA-sequencing. Results mbk-1 loss elicited global changes in transcription that were less pronounced in insulin-receptor mutant than in germline-deficient or wildtype C. elegans. Irrespective of genetic background, mbk-1 regulated genes were enriched for functions in biological processes related to organic acid metabolism and pathogen defense. qPCR-studies confirmed mbk-1 dependent induction of all three C. elegans Δ9-fatty acid desaturases, fat-5, fat-6 and fat-7, in wildtype, germline-deficient and insulin-receptor mutant strains. Conversely, mbk-1 dependent expression patterns of selected pathogen resistance genes, including asp-12, dod-24 and drd-50, differed across the genetic backgrounds examined. Finally, cth-1 and cysl-2, two genes which connect pathogen resistance to the metabolism of the gaseous messenger and lifespan regulator hydrogen sulfide (H2S), were commonly suppressed by mbk-1 loss only in wildtype and germline-deficient, but not in insulin-receptor mutant C. elegans. Conclusion Our work reveals previously unknown roles of C. elegans mbk-1 in the regulation of fatty acid desaturase- and H2S metabolic-genes. These roles are only partially dependent on genetic background. Considering the particular importance of fatty acid desaturation and H2S for longevity of germline-deficient C. elegans, we propose that these processes at least in part account for the previous observation that mbk-1 preferentially regulates lifespan in these worms.

scholarly journals Higher Plant Cytochrome b5 Polypeptides Modulate Fatty Acid Desaturation

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31370 ◽  
Author(s):  
Rajesh Kumar ◽  
Lam-Son Phan Tran ◽  
Anjanasree K. Neelakandan ◽  
Henry T. Nguyen
Keyword(s):  
Fatty Acid ◽  
Cytochrome B5 ◽  
Fatty Acid Desaturation ◽  
Higher Plant

Mutagenesis of the borage Δ6 fatty acid desaturase

2000 ◽  
Vol 28 (6) ◽  
pp. 636-638 ◽  
Author(s):  
O. Sayanova ◽  
F. Beaudoin ◽  
B. Libisch ◽  
P. Shewry ◽  
J. Napier
Keyword(s):  
Fatty Acid ◽  
Consensus Sequence ◽  
Fatty Acid Desaturase ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
The Third ◽  
Membrane Bound ◽  
Fusion Domain ◽  
Δ6 Desaturase

The consensus sequence of the third histidine box of a range of Δ5, Δ6, Δ8 and sphingolipid desaturases differs from that of the membrane-bound non-fusion Δ12 and Δ15 desaturases in the presence of glutamine instead of histidine. We have used site-directed mutagenesis to determine the importance of glutamine and other residues of the third histidine box and created a chimaeric enzyme to determine the ability of the Cyt b5 fusion domain from the plant sphingolipid desaturase to substitute for the endogenous domain of the Δ6 desaturase.

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