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

Science ◽  
2019 ◽  
Vol 366 (6461) ◽  
pp. 128-132 ◽  
Author(s):  
Aránzazu Gallego-García ◽  
Antonio J. Monera-Girona ◽  
Elena Pajares-Martínez ◽  
Eva Bastida-Martínez ◽  
Ricardo Pérez-Castaño ◽  
...  
Keyword(s):  
Vinyl Ether ◽  
Desaturase Activity ◽  
Bond Formation ◽  
Myxococcus Xanthus ◽  
Light Response ◽  
Human Cell Line ◽  
Photooxidative Stress ◽  
Ether Bond ◽  
Human Enzyme ◽  
Bacterial Enzyme

Plasmalogens are glycerophospholipids with a hallmark sn-1 vinyl ether bond. These lipids are found in animals and some bacteria and have proposed membrane organization, signaling, and antioxidant roles. We discovered the plasmanylethanolamine desaturase activity that is essential for vinyl ether bond formation in a bacterial enzyme, CarF, which is a homolog of the human enzyme TMEM189. CarF mediates light-induced carotenogenesis in Myxococcus xanthus, and plasmalogens participate in sensing photooxidative stress through singlet oxygen. TMEM189 and other animal homologs could functionally replace CarF in M. xanthus, and knockout of TMEM189 in a human cell line eliminated plasmalogens. Discovery of the human plasmanylethanolamine desaturase will spur further study of plasmalogen biogenesis, functions, and roles in disease.

scholarly journals C–C (alkynylation) vs C–O (ether) bond formation under Pd/C–Cu catalysis: synthesis and pharmacological evaluation of 4-alkynylthieno[2,3-d]pyrimidines

2011 ◽  
Vol 7 ◽  
pp. 338-345 ◽  
Author(s):  
Dhilli Rao Gorja ◽  
K Shiva Kumar ◽  
K Mukkanti ◽  
Manojit Pal
Keyword(s):  
Cytotoxic Activity ◽  
Catalytic System ◽  
High Selectivity ◽  
Bond Formation ◽  
Terminal Alkynes ◽  
Ether Bond ◽  
Pharmacological Evaluation

The Pd/C–CuI–PPh3 catalytic system facilitated C–C bond formation between 4-chlorothieno[2,3-d]pyrimidines and terminal alkynes in methanol with high selectivity without generating any significant side products arising from C–O bond formation between the chloro compounds and methanol. A variety of novel 4-alkynylthieno[2,3- d]pyrimidines were prepared via alkynylation of 4-chlorothieno[2,3-d]pyrimidines in good to excellent yields. Some of the compounds synthesized were tested for cytotoxic activity in vitro.

Specific Iodination of Vinyl Ether Bond

1969 ◽  
Vol 71 (8) ◽  
pp. 618-621
Author(s):  
C. V. Viswanathan ◽  
S. P. Hoevet ◽  
G. A. Muccini ◽  
W. O. Lundberg
Keyword(s):  
Vinyl Ether ◽  
Ether Bond

C-H Functionalization to Form C-O, C-N, and C-C Bonds

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Vinyl Ether ◽  
Boronic Acid ◽  
Bond Formation ◽  
University Of Maryland ◽  
Tsinghua University ◽  
Statistical Mixture ◽  
Mild Conditions ◽  
Hydride Abstraction ◽  
La Jolla ◽  
The University

A classic example of C-H functionalization is the familiar NBS bromination of a benzylic site. Recent updates of this approach allow for direct alkoxylation (J. Am. Chem. Soc. 2008, 130, 7824) and net amination (Organic Lett. 2008, 10, 1863). For the amination of simple aliphatic H’s, Holger F. Bettinger of Ruhr-Universität Bochum developed (Angew. Chem. Int. Ed. 2008, 47, 4744) the boryl azide 2. The insertion with 1 proceeded to give a statistical mixture of the nitrene insertion products 3 and 4. The tethered C-H functionalization devised (J. Am. Chem. Soc. 2008, 130, 7247) by Phil S. Baran of Scripps-La Jolla is selective, as in the conversion to 5 to 6, but appears to be limited to tertiary and benzylic C-H sites. Michael P. Doyle of the University of Maryland established (J. Org. Chem. 2008, 73, 4317) an elegant protocol for the oxidation of an alkyne such as 7 to the ynone 8. Note that the oxidation did not move the alkyne. Marta Catellani of the Università di Parma reported (Adv. Synth. Cat. 2008, 350, 565) the intriguing Pd-catalyzed conversion of 9 to 10. Under mild conditions, it might likely be possible to hydrolyze the vinyl ether to reveal the phenol 11. Another way of looking at this overall transformation would be to consider the ether 10 to be a protected form of the aldehyde 12. C-H activation can also lead to C-C bond formation. Irena S. Akhrem of the Nesmeyanov Institute, Moscow, described (Tetrahedron Lett. 2008, 49, 1399) a hydride-abstraction protocol for three-component coupling of a hydrocarbon 13 , an amine 14 , and CO, leading to the homologated amide 15. Hua Fu of Tsinghua University, Beijing, showed (J. Org. Chem. 2008 , 73, 3961) that oxidation of an amine 16 led to an intermediate that could be coupled with an alkyne 17 to give the propargylic amine 18. Products 15 and 18 are the result of sp2 and sp coupling, respectively. C-H functionalization leading to sp3 -sp3 coupling is less common. Jin-Quan Yu of Scripps/La Jolla found (J. Am. Chem. Soc. 2008, 130, 7190) that activation of the N-methoxy amide 19 in the presence of the alkyl boronic acid 20 gave smooth coupling, to 21.

scholarly journals TheTMEM189gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens

2020 ◽  
Vol 117 (14) ◽  
pp. 7792-7798 ◽  
Author(s):  
Ernst R. Werner ◽  
Markus A. Keller ◽  
Sabrina Sailer ◽  
Katharina Lackner ◽  
Jakob Koch ◽  
...  
Keyword(s):  
Double Bond ◽  
Vinyl Ether ◽  
Desaturase Activity ◽  
Immune Cell ◽  
Transmembrane Protein ◽  
Chemical Properties ◽  
Chronic Obstructive ◽  
Protein Motif ◽  
Obstructive Pulmonary Disease ◽  
Alternative Type

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.

Specific inhibition of ribonucleotide reductases by peptides corresponding to the C-terminal of their second subunit

1991 ◽  
Vol 69 (1) ◽  
pp. 79-83 ◽  
Author(s):  
Gregory Cosentino ◽  
Pierre Lavallée ◽  
Sumanas Rakhit ◽  
Raymond Plante ◽  
Yvon Gaudette ◽  
...  
Keyword(s):  
Ribonucleotide Reductase ◽  
Synthetic Peptide ◽  
Herpes Virus ◽  
Small Subunit ◽  
Terminal Sequence ◽  
E Coli ◽  
Ribonucleotide Reductases ◽  
Human Enzyme ◽  
Bacterial Enzyme ◽  
Herpès Virus

Previous studies have shown that herpes virus ribonucleotide reductase can be inhibited by a synthetic nonapeptide whose sequence is identical to the C-terminal of the small subunit of the enzyme. This peptide is able to interfere with normal subunit association that takes place through the C-terminal of the small subunit. In this report, we illustrate that inhibition of ribonucleotide reductases by peptides corresponding to the C-terminal of subunit R2 is also observed for the enzyme isolated from Escherichia coli, hamster, and human cells. The nonapeptide corresponding to the bacterial C-terminal sequence was found to inhibit E. coli enzyme with an IC50 of 400 μM, while this peptide had no effect on mammalian ribonucleotide reductase. A corresponding synthetic peptide derived from the C-terminal of the small subunit of the human enzyme inhibited both human and hamster ribonucleotide reductases with IC50 values of 160 and 120 μM, respectively. However, this peptide had no inhibitory activity against the bacterial enzyme. Equivalent peptides derived from herpes virus ribonucleotide reductase had no effect on either the bacterial or mammalian enzymes. Thus, subunit association at the C-terminal of the small subunit appears to be a common feature of ribonucleotide reductases. In addition, the inhibitory phenomenon observed with peptides corresponding to the C-terminal appears not only to be universal, but also specific to the primary sequence of the enzyme.Key words: ribonucleotide reductase, inhibition, human, bacteria.

Direct biosynthetic cyclization of a distorted paracyclophane highlighted by double isotopic labelling of l-tyrosine

2015 ◽  
Vol 13 (12) ◽  
pp. 3662-3666 ◽  
Author(s):  
Alexandre Ear ◽  
Séverine Amand ◽  
Florent Blanchard ◽  
Alain Blond ◽  
Lionel Dubost ◽  
...  
Keyword(s):  
Bond Formation ◽  
Aryl Ether ◽  
Isotopic Labelling ◽  
Ether Bond

The biosynthesis of pyrrocidines was investigated using a double (18O,13C) labelling of l-tyrosine. It shows that the phenolic 18O is incorporated during aryl ether bond formation.

Alkyl Aryl Ether Bond Formation with PhenoFluor

2015 ◽  
Vol 127 (19) ◽  
pp. 5754-5757 ◽  
Author(s):  
Xiao Shen ◽  
Constanze N. Neumann ◽  
Claudia Kleinlein ◽  
Nathaniel W. Goldberg ◽  
Tobias Ritter
Keyword(s):  
Bond Formation ◽  
Aryl Ether ◽  
Alkyl Aryl ◽  
Ether Bond

scholarly journals P450 monooxygenase ComJ catalyses side chain phenolic cross-coupling during complestatin biosynthesis

RSC Advances ◽  
2017 ◽  
Vol 7 (56) ◽  
pp. 35376-35384 ◽  
Author(s):  
Aurelio Mollo ◽  
A. Nikolai von Krusenstiern ◽  
Joshua A. Bulos ◽  
Veronika Ulrich ◽  
Karin S. Åkerfeldt ◽  
...  
Keyword(s):  
High Efficiency ◽  
Bond Formation ◽  
Cross Coupling ◽  
Side Chain ◽  
P450 Monooxygenase ◽  
Peptide Substrates ◽  
Ether Bond ◽  
Biaryl Ether

P450 monooxygenase enzyme ComJ catalyzed biaryl ether bond formation with high efficiency and low stereoselectivity on selected complestatin-like peptide substrates.

scholarly journals Eosinophil Peroxidase-derived Reactive Brominating Species Target the Vinyl Ether Bond of Plasmalogens Generating a Novel Chemoattractant, α-Bromo Fatty Aldehyde

2003 ◽  
Vol 278 (11) ◽  
pp. 8942-8950 ◽  
Author(s):  
Carolyn J. Albert ◽  
Arun K. Thukkani ◽  
Rita M. Heuertz ◽  
Arne Slungaard ◽  
Stanley L. Hazen ◽  
...  
Keyword(s):  
Vinyl Ether ◽  
Fatty Aldehyde ◽  
Ether Bond ◽  
Eosinophil Peroxidase
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