)-499.6 (Liu)-372.7 (H,)-372.7 (Wallace)-372.7 (KK,)-372.7 (Reynolds)-372.7 (KA)-372.7 (\(1997\))-372.7 (Linking)-372.7 (diversity)-372.7 (in)-372.7 (evolutionary)-372.7 (origin)-372.7 (and)]TJ Carboxylation reactions are essentially just aldol condensations, except that the carbonyl electrophile is CO 2 rather than a ketone or aldehyde. 1.8897 -1.1667 Td -1.8897 -1.1667 Td 1.8897 -1.1989 Td Herein, we report the copper-catalyzed oxidative dehydrogenative carboxylation (ODC) of unactivated alkanes in the presence of carboxylic acid derivatives to form the corresponding allylic ester (Scheme 1).This reaction is related to the classic Kharasch–Sosnovsky reaction, 24 but the starting material is an alkane, rather than an alkene. [(Chem)-293.6 (Commun)]TJ 3.6671 0 Td [(script,)-269.9 (Frederik)-269.9 (Golitsch)-269.9 (for)-269.9 (technical)-269.9 (assistance,)-269.9 (and)-269.9 (Ivan)-269.9 (Berg)-269.9 (and)-269.9 (Toma)]TJ )-499.6 (Lundberg)-269.5 (NN,)-269.4 (Thorpe)-269.4 (C)-269.4 (\(1993\))-269.4 (Inactivation)-269.4 (of)-269.4 (short-chain)-269.5 (acyl-coenzyme-A)-269.5 (dehydro-)]TJ )Tj )-499.6 (Li)-288.8 (F,)-288.8 (et)-288.9 (al. To investigate the mechanism of carboxylation, the oxidation of NADPH in a mixture of crotonyl-CoA * and Ccr was followed spectrophotometrically at 360 nm upon the addition of either CO 2 or HCO 3−. 29.4878 0 Td )]TJ (34:1163\2261176. /T1_1 1 Tf [(53. [(alkenal/one)-299.8 (oxidoreductase. [(Adv)-314.4 (Synth)-314.4 (Catal)]TJ /T1_1 1 Tf 33.3202 0 Td [(enoyl)-475.9 (reductase,)-475.9 (modulates)-475.9 (the)-475.9 (conformation)-475.9 (of)-475.9 (the)-475.9 (NADH)-475.9 (cofactor)-475.9 (to)-475.9 (promote)]TJ [(Streptomyces)-536 (coelicolor)]TJ [(Mycobacterium)-293.6 (tuberculosis. [(J)-310.6 (Am)-310.7 (Chem)-310.7 (Soc)]TJ [(Enzymatic)-530.8 (Reaction)-530.8 (Mechanism)]TJ -6.8897 -1.2008 Td [(2. )-195.1 (\(1996\))-195.1 (Structural)-195.1 (and)-195.1 (sequence)-195.1 (comparisons)-195.1 (of)-195.1 (quinone)-195.1 (oxidoreduc-)]TJ (R)Tj /T1_1 1 Tf -35.7666 -1.1667 Td (2)Tj /T1_1 1 Tf The formation of disulfide bonds in specific configurations is often important to the structure, function, or stability of the biopharmaceutical protein. )-239.5 (For)]TJ [-0.3 (,)-258.5 (respectively. (doi)Tj [(We)-174.5 (thank)-174.5 (D.A. /T1_4 1 Tf )Tj /T1_7 1 Tf You can think of a carboxylation reaction as essentially a special kind of aldol reaction, except that the carbonyl electrophile being attacked by the enolate is \(CO_2\) rather than a ketone or aldehyde: Mechanism for carboxylation of an enolate. (243:3857\2263863. /T1_1 1 Tf (328:173\226183. [(45. [(Escherichia)-481.6 (coli)]TJ <>/Font<>/ProcSet[/PDF/Text/ImageB/ImageC]/XObject<>>>/Rotate 0/TrimBox[9 9 603 792]/Type/Page>> 12.3242 0 Td 1.8896 -1.2008 Td (sphaeroides)Tj [(129:6425\226)-119.8 (6431. 6.5 0 0 6.5 80.2973 39.8835 Tm (A3\(2\). [(52. Figure 15.12. 26.9186 0 Td 7 0 0 7 51.6761 735.8835 Tm (Rhodobacter)Tj -24.5023 -1.2008 Td 3.3568 0 Td Biesalski, in Reference Module in Food Science, 2016. 13.5929 0 Td 5.7803 0 Td 75 0 obj [(from)-263.4 (the)-263.4 (reaction)-263.4 (mixture. This number matters since the RubisCO reacts with CO2 in the aqueous phase. uuid:bc3eb447-1dd1-11b2-0a00-b80000000000 6 0 0.9318 6 227.8851 527.875 Tm 39 Beyond 200 °C, however, the reaction yielded a mixture of C3, C2, and C7 carboxylation products. Several biopharmaceutical proteins (such as recombinant factor IX and recombinant factor VIIa) undergo γ-carboxylation within certain highly conserved sequences in the N-terminal domain (Gla domain). )Tj [(SI)-267.5 (Methods)]TJ 0 -1.1648 TD [(Chem)-326.8 (Rev)]TJ /T1_2 1 Tf )]TJ -0.0195 Tc 7 0 0 7 109.9147 717.8835 Tm The analysis of disulfide bond structure is discussed in more detail in Section II.A.2. Since the biotin is attached to the carrier protein by a long flexible hydrocarbon chain, it reacts alternately with the carboxylase and carboxyl transferase in this multienzyme complex (Fig. [(nases/reductases)-243.4 (\(MDR\)\227Sub-lines)-243.4 (including)]TJ Preliminary data suggests the mechanism involves two discrete nickel-mediated catalytic cycles, the first involving a catalyzed hydrozincation of the alkene followed by a second, slower nickel-catalyzed carboxylation of the in situ formed organozinc reagent. (327:47\22659. 6 0 0 6 81.4306 283.1023 Tm -23.8364 -1.1648 Td )]TJ Mechanistic studies suggest that step (1) occurs by the phosphorylation of bicarbonate to form carboxyphosphate, which carboxylates the enolate of biotin possibly via bound CO 2 as an intermediate. Similar experiments on the reductive carboxylation of pyruvate catalysed by the `malic' enzyme show that dissolved CO 2 is the primary substrate of this enzyme also. [(Cryptic)-387.2 (Stereochemistry)-387.2 (at)-387.2 (C3)-387.2 (\(Reductase)-387.2 (Reaction\). (Miscellaneous. 9.9717 0 Td The conversion of Glu to Gla creates the ability to chelate Ca2+, which is essential to the function of the γ-carboxylated proteins. )Tj [(J)-293.6 (Biol)-293.6 (Chem)]TJ γ-Carboxylation is a PTM carried out by the enzyme γ-glutamyl carboxylase during the biosynthesis of vitamin K-dependent proteins (Stenflo and Suttie, 1977). )-499.6 (Heath)-247.2 (RJ,)-247.2 (Rock)-247.2 (CO)-247.2 (\(2000\))-247.2 (A)-247.2 (triclosan-resistant)-247.2 (bacterial)-247.2 (enzyme. I. Lindberg, J.R. Peinado, in Encyclopedia of Cell Biology, 2016. γ-Carboxylation is a PTM carried out by the enzyme γ-glutamyl carboxylase during the biosynthesis of vitamin K-dependent proteins (Stenflo and Suttie, 1977). [(Biochem)-305.5 (J)]TJ (substrates. /T1_2 1 Tf /T1_2 1 Tf )-499.6 (Sprecher)-154.4 (M,)-154.4 (Clark)-154.4 (MJ,)-154.4 (Sprinson)-154.4 (DB)-154.4 (\(1966\))-154.4 (The)-154.4 (absolute)-154.4 (con\036guration)-154.4 (of)-154.4 (methylmalonyl)]TJ The widespread distribution of both Gla and γ-carboxylase activity supports the idea that this PTM plays other, less well-understood biological roles (Kulman et al., 2007). 5. /T1_1 1 Tf -1.8897 -1.2008 Td 5.0001 0 Td In these cell-based assays, different vitamin K-dependent proteins were designed and stably expressed in mammalian cells as reporter proteins to accommodate the readily used enzyme-linked immunosorbent assay for carboxylation efficiency evaluation. 15.6502 0 Td 37.1534 0 Td (283:32283\22632293. 0 -1.2008 TD /T1_6 1 Tf )Tj Acetyl CoA carboxylase is also present outside the plastids, probably in the cytosol. [(1\226)-119.8 (89. [-0.1 (\002)]TJ 1.8897 -1.1667 Td /T1_1 1 Tf )Tj (H]-C)Tj -1.8897 -1.2008 Td 1.8897 -1.2008 Td The sulfhydryl group of the Cys residue can form a covalent disulfide bond with another sulfhydryl. 4.5 0 0 4.5 173.0818 471.2159 Tm )-499.6 (Fillgrove)-231.1 (KL,)-231.1 (Anderson)-231.1 (VE)-231.1 (\(2000\))-231.1 (Orientation)-231.1 (of)-231.1 (coenzyme)-231.1 (A)-231.1 (substrates,)-231.1 (nicotinamide)]TJ )Tj /T1_2 1 Tf /T1_1 1 Tf Given the very low acidity of the C–H bond at C3 (Δ acid H° = 397 kcal mol −1, Fig. )Tj [(Heidelberg\),)-278 (4th)-278 (edition,)-278 (pp)-278 (1\22628)-278 (and)-278 (pp)-278 (177\226219. /T1_1 1 Tf [(275:40128)-119.8 (\226)-119.8 (40133. -28.626 -1.1667 Td 9.7567 0 Td )-233.4 (The)-233.4 (crotonyl-CoA)-233.4 (formed)-233.4 (was)-233.4 (analyzed)-233.4 (by)-233.4 (HPLC-MS)]TJ In addition to carboxylic acids, lactones were formed when ricinoleic acid or linoleic acid was used in the reaction.204,208, J.-K. )]TJ )-499.8 (Erb)-234.4 (TJ,)-234.4 (et)-234.4 (al. 1.3338 -1.1648 Td )-499.6 (Bell)-252.9 (AF,)-252.9 (et)-252.9 (al. However, evidence suggests that the immediate reactive species that carboxylates biotin is carboxyphosphate, as in the (biotin-independent) reaction of carbamyl phosphate synthetase in urea and pyrimidine synthesis. 1.8897 -1.1648 Td [(190:843\226)-119.8 (850. -0.0195 Tc 7 0 0 7 226.2096 680.8835 Tm /T1_1 1 Tf /T1_1 1 Tf 18.7323 0 Td /T1_2 1 Tf [(Stereospecificity)-332.4 (of)-332.4 (the)-332.4 (Hydrogen)-332.4 (Transfer)-332.4 (from)-332.4 (NADPH)-332.4 (\(Reductase)-332.4 (Reaction\). Such metabolites detected in the urine suggest biotin-depletion at the tissue-level in individuals without congenital metabolic disorders). /T1_1 1 Tf -26.1502 -1.2008 Td )-288.8 (\(2008\))-288.8 (Coupled)-288.9 (ferredoxin)-288.9 (and)-288.9 (crotonyl)-288.8 (coenzyme)-288.9 (A)-288.9 (\(CoA\))-288.8 (reduction)-288.9 (with)]TJ -10.3318 -1.2857 Td 0 -1.1989 TD 6.4165 0 Td 0.0284 Tc -6.8897 -1.1667 Td Due to photosynthesis, the CO2 concentration decreases until it reaches a concentration at which the fixation of CO2 and the release of CO2 are counterbalanced. Figure 15.11. The intermediate will have a proton abstracted by a water molecule and the ethoxy group will be protonated (it can happen either by intermolecular reaction with an H3O+ or by an intramolecular reaction with a proton migration from the protonated intermediate after the water attack). [(-unsaturated)-394 (carbonyl)]TJ 0 Tc 0.5002 0 Td )Tj [(acyl)-536 (carrier)-536 (protein)-536 (reductase)-536 (from)]TJ 2009-05-28T13:25:09Z -0.0195 Tc 2.7711 0 Td (459. (2)Tj )-499.6 (Smith)-300.2 (S,)-300.2 (Tsai)-300.2 (S-C)-300.2 (\(2007\))-300.2 (The)-300.2 (type)-300.2 (I)-300.2 (fatty)-300.2 (acid)-300.2 (and)-300.2 (polyketide)-300.2 (synthases:)-300.2 (A)-300.2 (tale)-300.2 (of)-300.2 (two)]TJ 6.9675 0 Td 5.0704 0 Td (\003)Tj 10.8099 0 Td [(15. )Tj /T1_1 1 Tf [(enzymatic)-278 (dehydration)-278 (of)-278 (butyryl)-278 (coenzyme)-278 (A. 4.5 0 0 4.5 274.5265 284.8523 Tm /T1_1 1 Tf 1.8897 -1.1667 Td /T1_2 1 Tf 1.3338 -1.1648 Td /T1_1 1 Tf The carboxylation of acetyl CoA involves biotin which acts as a carrier for “activated CO2” (Fig.