A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis

Gallego-García, Aránzazu; Monera-Girona, Antonio J.; Pajares-Martínez, Elena; Bastida‐Martínez, Eva; Pérez‐Castaño, Ricardo; Iniesta, Antonio A.; Fontes, Marta; Padmanabhan, S.; Elías‐Arnanz, Montserrat

doi:10.1126/science.aay1436

Cited by 90 publications

(128 citation statements)

References 40 publications

(51 reference statements)

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“…Among them, plasmanyl desaturase (1′-alkyl desaturase) is a predicted unstable membrane enzyme that remains to be identified for many years. In a recent report, the enzyme CarF found in an aerobic bacterium Myxobacteria was confirmed to be the 1′-alkyl desaturase for the last step of plasmalogen formation ( Gallego-García et al, 2019 ). Its homolog TMEM189 was successively identified in mice and human ( Gallego-García et al, 2019 ; Werner et al, 2020 ).…”

Section: The Oxygen-dependent Pathway Of Plasmalogens Biosynthesismentioning

confidence: 97%

“…In a recent report, the enzyme CarF found in an aerobic bacterium Myxobacteria was confirmed to be the 1′-alkyl desaturase for the last step of plasmalogen formation ( Gallego-García et al, 2019 ). Its homolog TMEM189 was successively identified in mice and human ( Gallego-García et al, 2019 ; Werner et al, 2020 ). Knock out of the animal homolog in human cell lines resulted in the deficiency of plasmalogens, indicating that TMEM189 is needed to catalyze the final step in plasmalogen synthesis in human cells ( Gallego-García et al, 2019 ).…”

Section: The Oxygen-dependent Pathway Of Plasmalogens Biosynthesismentioning

confidence: 97%

“…Its homolog TMEM189 was successively identified in mice and human ( Gallego-García et al, 2019 ; Werner et al, 2020 ). Knock out of the animal homolog in human cell lines resulted in the deficiency of plasmalogens, indicating that TMEM189 is needed to catalyze the final step in plasmalogen synthesis in human cells ( Gallego-García et al, 2019 ).…”

Section: The Oxygen-dependent Pathway Of Plasmalogens Biosynthesismentioning

confidence: 99%

“…Plasmalogens evolved first in anaerobic bacteria, but they are absent in facultative and aerobic bacteria except for Myxobacteria, which were recently found to use an oxygen-dependent synthetic pathway ( Lorenzen et al, 2014 ; Gallego-García et al, 2019 ). Plasmalogens are not found in fungi or plants ( Goldfine, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

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Advances in the Biosynthetic Pathways and Application Potential of Plasmalogens in Medicine

Zhou

Zhao

et al. 2020

Front. Cell Dev. Biol.

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Plasmalogens are a special class of polar glycerolipids containing a vinyl-ether bond and an ester bond at sn-1 and sn-2 positions of the glycerol backbone, respectively. In animals, impaired biosynthesis and regulation of plasmalogens may lead to certain neurological and metabolic diseases. Plasmalogens deficiency was proposed to be strongly associated with neurodegenerative and metabolic diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and appropriate supplement of plasmalogens could help to prevent and possibly provide therapy of these diseases. Plasmalogens evolved first in anaerobic bacteria with an anaerobic biosynthetic pathway. Later, an oxygen-dependent biosynthesis of plasmalogens appeared in animal cells. This review summarizes and updates current knowledge of anaerobic and aerobic pathways of plasmalogens biosynthesis, including the enzymes involved, steps and aspects of the regulation of these processes. Strategies for increasing the expression of plasmalogen synthetic genes using synthetic biology techniques under specific conditions are discussed. Deep understanding of plasmalogens biosynthesis will provide the bases for the use of plasmalogens and their precursors as potential therapeutic regimens for age-related degenerative and metabolic diseases.

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Section: The Oxygen-dependent Pathway Of Plasmalogens Biosynthesismentioning

confidence: 97%

Section: The Oxygen-dependent Pathway Of Plasmalogens Biosynthesismentioning

confidence: 97%

Section: The Oxygen-dependent Pathway Of Plasmalogens Biosynthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Advances in the Biosynthetic Pathways and Application Potential of Plasmalogens in Medicine

Zhou

Zhao

et al. 2020

Front. Cell Dev. Biol.

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“…Note Added in Proof. A recent study characterizing a bacterial light response also found that the TMEM189 gene encodes PEDS (44).…”

Section: Harvest Of Mouse Tissues For Analysis Of Peds Activity and Pmentioning

confidence: 95%

The TMEM189 gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens

Werner

Keller

Sailer

et al. 2020

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

104

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A significant fraction of the glycerophospholipids in the human body is composed of plasmalogens, particularly in the brain, cardiac, and immune cell membranes. A decline in these lipids has been observed in such diseases as Alzheimer’s and chronic obstructive pulmonary disease. Plasmalogens contain a characteristic 1-O-alk-1′-enyl ether (vinyl ether) double bond that confers special biophysical, biochemical, and chemical properties to these lipids. However, the genetics of their biosynthesis is not fully understood, since no gene has been identified that encodes plasmanylethanolamine desaturase (E.C. 1.14.99.19), the enzyme introducing the crucial alk-1′-enyl ether double bond. The present work identifies this gene as transmembrane protein 189 (TMEM189). Inactivation of theTMEM189gene in human HAP1 cells led to a total loss of plasmanylethanolamine desaturase activity, strongly decreased plasmalogen levels, and accumulation of plasmanylethanolamine substrates and resulted in an inability of these cells to form labeled plasmalogens from labeled alkylglycerols. Transient expression of TMEM189 protein, but not of other selected desaturases, recovered this deficit. TMEM189 proteins contain a conserved protein motif (pfam10520) with eight conserved histidines that is shared by an alternative type of plant desaturase but not by other mammalian proteins. Each of these histidines is essential for plasmanylethanolamine desaturase activity. Mice homozygous for an inactivatedTmem189gene lacked plasmanylethanolamine desaturase activity and had dramatically lowered plasmalogen levels in their tissues. These results assign theTMEM189gene to plasmanylethanolamine desaturase and suggest that the previously characterized phenotype ofTmem189-deficient mice may be caused by a lack of plasmalogens.

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Metabolome‐Based Genome‐Wide Association Study of Duck Meat Leads to Novel Genetic and Biochemical Insights

et al. 2023

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Meat is among the most consumed foods worldwide and has a unique flavor and high nutrient density in the human diet. However, the genetic and biochemical bases of meat nutrition and flavor are poorly understood. Here, 3431 metabolites and 702 volatiles in 423 skeletal muscle samples are profiled from a gradient consanguinity segregating population generated by Pekin duck × Liancheng duck crosses using metabolomic approaches. The authors identified 2862 metabolome‐based genome‐wide association studies (mGWAS) signals and 48 candidate genes potentially modulating metabolite and volatile levels, 79.2% of which are regulated by cis‐regulatory elements. The level of plasmalogen is significantly associated with TMEM189 encoding plasmanylethanolamine desaturase 1. The levels of 2‐pyrrolidone and glycerophospholipids are regulated by the gene expression of AOX1 and ACBD5, which further affects the levels of volatiles, 2‐pyrrolidone and decanal, respectively. Genetic variations in GADL1 and CARNMT2 determine the levels of 49 metabolites including L‐carnosine and anserine. This study provides novel insights into the genetic and biochemical basis of skeletal muscle metabolism and constitutes a valuable resource for the precise improvement of meat nutrition and flavor.

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A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis

Cited by 90 publications

References 40 publications

Advances in the Biosynthetic Pathways and Application Potential of Plasmalogens in Medicine

Advances in the Biosynthetic Pathways and Application Potential of Plasmalogens in Medicine

The TMEM189 gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens

Metabolome‐Based Genome‐Wide Association Study of Duck Meat Leads to Novel Genetic and Biochemical Insights

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