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1.
Dr. Feryel Soualmia Alain Guillot Dr. Nazarii Sabat Clémence Brewee Dr. Xavier Kubiak Dr. Michael Haumann Dr. Xavier Guinchard Dr. Alhosna Benjdia Dr. Olivier Berteau 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(31):e202200627
B12-dependent radical SAM enzymes are an emerging enzyme family with approximately 200,000 proteins. These enzymes have been shown to catalyze chemically challenging reactions such as methyl transfer to sp2- and sp3-hybridized carbon atoms. However, to date we have little information regarding their complex mechanisms and their biosynthetic potential. Here we show, using X-ray absorption spectroscopy, mutagenesis and synthetic probes that the vitamin B12-dependent radical SAM enzyme TsrM catalyzes not only C- but also N-methyl transfer reactions further expanding its synthetic versatility. We also demonstrate that TsrM has the unique ability to directly transfer a methyl group to the benzyl core of tryptophan, including the least reactive position C4. Collectively, our study supports that TsrM catalyzes non-radical reactions and establishes the usefulness of radical SAM enzymes for novel biosynthetic schemes including serial alkylation reactions at particularly inert C−H bonds. 相似文献
2.
Xiaolin Pei Qiuyan Wang Xiaofeng Qiu Longbin Ying Junhua Tao Tian Xie 《Applied biochemistry and biotechnology》2010,162(5):1423-1434
2-Deoxyribose-5-phosphate aldolase (DERA) catalyzes a sequential aldol reaction useful in synthetic chemistry. In this work,
the effect of a feeding strategy on the production of a thermophilic DERA was investigated in fed-batch cultures of recombinant
Escherichia coli BL21 (pET303-DERA008). The predetermined specific growth rate (μ
set) was evaluated at 0.20, 0.15, and 0.10 h−1, respectively. The DERA concentration and volumetric productivity were associated with μ
set. The cells synthesized the enzyme most efficiently at μ
set = 0.15 h−1. The maximum enzyme concentration (5.12 g/L) and total volumetric productivity (0.256 g L−1 h−1) obtained were over 10 and five times higher than that from traditional batch cultures. Furthermore, the acetate concentration
remained at a relatively low level, less than 0.4 g/L, under this condition which would not inhibit cell growth and target
protein expression. Thus, a specific growth rate control strategy has been successfully applied to induce fed-batch cultures
for the maximal production of the thermophilic 2-deoxyribose-5-phosphate aldolase. 相似文献
3.
Laura Iturrate Dr. Israel Sánchez‐Moreno Dr. Isabel Oroz‐Guinea Jesús Pérez‐Gil Dr. Eduardo García‐Junceda Dr. 《Chemistry (Weinheim an der Bergstrasse, Germany)》2010,16(13):4018-4030
A bifunctional aldolase/kinase enzyme named DLF has been constructed by gene fusion through overlap extension. This fusion enzyme consists of monomeric fructose‐1,6‐bisphosphate aldolase (FBPA) from Staphylococcus carnosus and the homodimeric dihydroxyacetone kinase (DHAK) from Citrobacter freundii CECT 4626 with an intervening linker of five amino acid residues. The fusion protein was expressed soluble and retained both kinase and aldolase activities. The secondary structures of the bifunctional enzyme and the parental enzymes were analyzed by circular dichroism (CD) spectroscopy to study the effect of the covalent coupling of the two parent proteins on the structure of the fused enzyme. Because S. carnosus FBPA is a thermostable protein, the effect of the fusion on the thermal stability of the bifunctional enzyme has also been studied. The proximity of the active centers in the fused enzyme promotes a kinetic advantage as the 20‐fold increment in the initial velocity of the overall aldol reaction indicates. Experimental evidence supports that this increase in the reaction rate can be explained in terms of substrate channeling. 相似文献
4.
Angela Kinnell Thomas Harman Matilda Bingham Alan Berry Adam Nelson 《Tetrahedron》2012,68(37):7719-7722
A one-pot, three-component process is described which involves both organo- and enzyme-catalysed carbon–carbon bond-forming steps. In the first step, an organocatalyst catalyses the aldol reaction between acetaldehyde and a glyoxylamide. After dilution with additional aqueous buffer, and addition of pyruvate and an aldolase enzyme variant, a second aldol reaction occurs to yield a final product. Crucially, it was possible to develop a reaction in which both the organo- and enzyme-catalysed reactions could be performed in the same aqueous buffer system. The reaction described is the first example of a one-pot, three-component reaction in which the two carbon–carbon bond-forming processes are catalysed using the combination of an organocatalyst and an enzyme. 相似文献
5.
Directed in vitro evolution can create RNA catalysts for a variety of organic reactions, supporting the "RNA world" hypothesis, which proposes that metabolic transformations in early life were catalyzed by RNA molecules rather than proteins. Among the most fundamental carbon-carbon bond-forming reactions in nature is the aldol reaction, mainly catalyzed by aldolases that utilize either an enamine mechanism (class I) or a Zn(2+) cofactor (class II). We report on isolation of a Zn(2+)-dependent ribozyme that catalyzes an aldol reaction at its own modified 5' end with a 4300-fold rate enhancement over the uncatalyzed background reaction. The ribozyme can also act as an intermolecular catalyst that transfers a biotinylated benzaldehyde derivative to the aldol donor substrate, coupled to an external hexameric RNA oligonucleotide, supporting the existence of RNA-originated biosynthetic pathways for metabolic sugar precursors and other biomolecules. 相似文献
6.
Xu Gong Juan Huang Xiangrui Sun Ziling Chen Prof. Dr. Ming Yang 《Angewandte Chemie (International ed. in English)》2023,62(31):e202306367
Illicium sesquiterpenes are a large family of biologically active secondary metabolites isolated from Illicium species of plants and are well-known for their activity of neurite outgrowth in cultured neurons. Herein, we propose a comprehensive biosynthetic pathway for illicium sesquiterpenes and report a synthetic route to illisimonin A and merrilactone A based on it. We think that the carbon scaffolds of most of the illicium sesquiterpenes could be synthesized from a dicarbonyl derivative of allo-cedrane through retro-Dieckmann condensation, oxidative cleavage and aldol reaction at suitable oxidation states in Nature. The common intermediate for illisimonin A and merrilactone A similar to the dicarbonyl derivative of allo-cedrane was assembled with up to 82 % ee by an asymmetric intramolecular desymmetrizing reductive Heck reaction by the use of a new type of chiral phosphine ligand. The syntheses of illisimonin A and merrilactone A supported the key transformations of the proposed biosynthetic pathway. 相似文献
7.
Robert M. Archer Dr. Sylvain F. Royer William Mahy Dr. Caroline L. Winn Prof. Michael J. Danson Dr. Steven D. Bull 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(8):2895-2902
Practical syntheses of 2‐keto‐3‐deoxy‐D ‐xylonate (D ‐KDX) and 2‐keto‐3‐deoxy‐L ‐arabinonate (L ‐KDA) that rely on reaction of the anion of ethyl 2‐[(tert‐butyldimethylsilyl)oxy]‐2‐(dimethoxy phosphoryl) acetate with enantiopure glyceraldehyde acetonide, followed by global deprotection of the resultant O‐silyl‐enol esters, have been developed. This has enabled us to confirm that a 2‐keto‐3‐deoxy‐D ‐gluconate aldolase from the archaeon Sulfolobus solfataricus demonstrates good activity for catalysis of the retro‐aldol cleavage of both these enantiomers to afford pyruvate and glycolaldehyde. The stereochemical promiscuity of this aldolase towards these enantiomeric aldol substrates confirms that this organism employs a metabolically promiscuous pathway to catabolise the C5‐sugars D ‐xylose and L ‐arabinose. 相似文献
8.
Nature has perfected the stereospecific aldol reaction by using aldolase enzymes. While virtually all the biochemical aldol reactions use unmodified donor and acceptor carbonyls and take place under catalytic control in an aqueous environment, the chemical domain of the aldol addition has mostly relied on prior transformation of carbonyl substrates, and the whole process traditionally is carried out in anhydrous solvents. The area of aqua-asymmetric aldol reactions has received much attention recently in light of the perception both of its green chemistry advantages and its analogy to eon-perfected enzyme catalysis. Both chiral metal complexes and small chiral organic molecules have been recently reported to catalyze aldol reactions with relatively high chemical and stereochemical efficiency. This tutorial review describes recent developments in this area. 相似文献
9.
10.
Directed evolution of D-2-keto-3-deoxy-6-phosphogluconate aldolase to new variants for the efficient synthesis of D- and L-sugars 总被引:2,自引:0,他引:2
BACKGROUND: Exploitation and improvement of enzymes as catalysts for organic synthesis is of current interest in biocatalysis. A representative enzyme for investigation is the Escherichia coli D-2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, which catalyzes the highly specific reversible aldol reaction using the D-configurated KDPG as substrate. RESULTS: Using in vitro evolution, the aldolase has been converted into aldolases with improved catalytic efficiency, altered substrate specificity and stereoselectivity. In particular, some evolved aldolases capable of accepting both D- and L- glyceraldehyde in the non-phosphorylated form as substrates for reversible aldol reaction have been obtained, providing a new direction to the enzymatic synthesis of both D- and L-sugars. CONCLUSIONS: This research has demonstrated the effectiveness of using in vitro evolution to rapidly alter the properties of an aldolase to improve its utility in asymmetric synthesis. The evolved aldolases, differing from the native enzyme which is highly phosphate- and D-sugar-dependent, catalyze the efficient synthesis of both D- and L-sugars from non-phosphorylated aldehydes and pyruvate. The principles and strategies described in this study should be applicable to other aldolases to further expand the scope of their synthetic utility. 相似文献
11.
Abstract Sphydrofuran (1) has been synthesized via a short chemo-enzymatic approach starting from achiral precursors. Rabbit muscle aldolase (RAMA)-promoted aldol condensation between dihydroxyacetone phosphate (DHAP) and chloroacetaldehyde yielded the D-threo-pentulose derivative 3. After suitable protection of the hydroxyl functions of 3, sphydrofuran could be obtained via a highly diastereoselective Grignard addition of allylmagnesium bromide followed by a Wacker reaction. 相似文献
12.
Kristina V. Goncharenko Sebastian Flückiger Dr. Cangsong Liao Dr. David Lim Anja R. Stampfli Prof. Dr. Florian P. Seebeck 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(6):1328-1334
Sulfoxide synthases are non-heme iron enzymes that participate in the biosynthesis of thiohistidines, such as ergothioneine and ovothiol A. The sulfoxide synthase EgtB from Chloracidobacterium thermophilum (CthEgtB) catalyzes oxidative coupling between the side chains of N-α-trimethyl histidine (TMH) and cysteine (Cys) in a reaction that entails complete reduction of molecular oxygen, carbon–sulfur (C−S) and sulfur–oxygen (S−O) bond formation as well as carbon–hydrogen (C−H) bond cleavage. In this report, we show that CthEgtB and other bacterial sulfoxide synthases cannot efficiently accept selenocysteine (SeCys) as a substrate in place of cysteine. In contrast, the sulfoxide synthase from the filamentous fungus Chaetomium thermophilum (CthEgt1) catalyzes C−S and C−Se bond formation at almost equal efficiency. We discuss evidence suggesting that this functional difference between bacterial and fungal sulfoxide synthases emerges from different modes of oxygen activation. 相似文献
13.
Takao Tsuneda Hiroki Sumitomo Masatoshi Hasebe Takuro Tsutsumi Tetsuya Taketsugu 《Journal of computational chemistry》2023,44(2):93-104
It is established that the reactive orbital energy theory (ROET) theoretically reproduces the rule-based electronic theory diagrams of organic chemistry by a comparative study on the charge transfer natures of typical organic carbon–carbon and carbon–heteroatom bond formation reactions: aldol, Mannich, α-aminooxylation, and isogyric reactions. The ROET, which is an expansion of the reaction electronic theories (e.g., the frontier orbital theory) in terms of orbital energies, elucidates the reactive orbitals driving reactions and the charge transferability indices of the reactions. Performing the ROET analyses of these reactions shows that the charge transfer directions given in the rule-based diagrams of the electronic theory are reproduced even for the functional groups of charge transfer destinations in all but only two processes for 38 reaction processes. The ROET analyses also make clear the detailed orbital-based pictures of these bond formation reactions: that is, the use of the out-of-plane antibonding π orbitals in acidic conditions (enol-mode) and in-plane antibonding π orbitals in basic conditions (enolate-mode), which explain the experimentally assumed mechanisms such as the π-bond formations in acidic conditions and σ-bond formations at α-carbons in basic conditions. Furthermore, the ROET analyses explicate that the methyl group initially accepts electrons and then donates them to the bond formations in the target reactions. It is, consequently, suggested that the ROET serves a theoretical foundation for the electronic theory of organic chemistry. 相似文献
14.
16O/18O Exchange of Aldehydes and Ketones caused by H218O in the Mechanistic Investigation of Organocatalyzed Michael,Mannich, and Aldol Reactions
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Prof. Dr. Yujiro Hayashi Dr. Takasuke Mukaiyama Dr. Meryem Benohoud Dr. Nishant R. Gupta Tsuyoshi Ono Shunsuke Toda 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(17):5868-5872
Organocatalyzed Michael, Mannich, and aldol reactions of aldehydes or ketones, as nucleophiles, have triggered several discussions regarding their reaction mechanism. H218O has been utilized to determine if the reaction proceeds through an enamine or enol mechanism by monitoring the ratio of 18O incorporated into the final product. In this communication, we describe the risk of H218O as an evaluation tool for this mechanistic investigation. We have demonstrated that exchange of 16O/18O occurs in the aldehyde or ketone starting material, caused by the presence of H218O and amine catalysts, before the Michael, Mannich, and aldol reactions proceed. Because the newly generated 18O starting aldehydes or ketones and 16O water affect the incorporation ratio of 18O in the final product, the use of H218O would not be appropriate to distinguish the mechanism of these organocatalyzed reactions. 相似文献
15.
The direct aldol reaction between a protected dihydroxyacetone derivative and 4-nitrobenzaldehyde catalyzed by chiral Zn2+ complexes of 1-(n-carboxylalkyl)-7-aminoacyl-1,4,7,10-tetraazacyclododecane is reported. New Zn2+ complexes containing l-histidine and carboxylalkyl chains that mimic a class II aldolase, carboxypeptidase A and a serine protease were designed and synthesized. Syn-aldol products were mainly formed by an aldol reaction of acetonide-protected dihydroxyacetone with benzaldehydes and other benzaldehydes in N-methylpyrrolidone (NMP)/alcohol (MeOH, EtOH or 2-PrOH) in good yields with a high degree of diastereo- and enantioselectivity (56%~quant., 57~>99% ee). Mechanistic aspect based on ESI-HRMS, elemental analysis and pH titrations of model ligands is also discussed. 相似文献
16.
Craig S. Haynes Cassie A. Goodman Juandah Bruce Sarah C. Genin Brad J. Austermuehle Victor L. Leong Austin R. Leise Robert Larson Christopher G. Hamaker Shawn R. Hitchcock 《Tetrahedron: Asymmetry》2017,28(1):98-104
An N3-(p-methoxyphenoxy)acetyloxazolidine-2-thione has been synthesized and employed in glycolate asymmetric aldol addition reactions with aromatic and aliphatic aldehydes. It was determined that the titanium tetrachloride medicated aldol reaction afforded diastereoselectivities that ranged from 75:25 to 94:6 when the reaction was conducted at ?78 °C. The absolute stereochemistry of the aldol adducts was determined by 1H NMR spectroscopy and X-ray crystallography. The 1H NMR spectra of the aldol adducts contained a signal (the α-proton of the glycolate position of the aldol side chain) that was highly deshielded due to conformational restriction about the N(3)-(p-methoxyphenoxy)acetyl side chain and the oxazolidine-2-thione auxiliary. 相似文献
17.
Horst Glaser Ralph Puchta NicoJ.R. vanEikemaHommes Dirk Leusser Alexander Murso Dietmar Stalke Walter Bauer RolfW. Saalfrank 《Helvetica chimica acta》2002,85(11):3828-3841
It has been found by serendipity during the attempted synthesis of the potential tris‐bidentate ligand 7 that this compound undergoes multiple ring‐closure reactions to form the heterodamantane derivative 12 . This reaction involves a domino aldol addition/hemiketal formation/hemiketal formation/epimerization sequence. Compound 12 was studied intensively by X‐ray crystal‐structure analysis, NMR, and AM1 computations. Complete assignment of all 1H‐ and 13C‐NMR signals was achieved by a combination of HMQC, HMBC, DPFGSE‐NOE, COSY, and long‐range‐COSY experiments. The NMR data agreed well with the crystallographic and computational results. Accordingly, 12 is present as the thermodynamically most‐stable diastereoisomer with relative u‐configuration at centers C(8) and C(9). In summary, five stereogenic centers were created starting from an achiral precursor in an efficient cascade reaction under thermodynamic control. 相似文献
18.
Total Synthesis of the 7,10‐Epimer of the Proposed Structure of Amphidinolide N,Part I: Synthesis of the C1–C13 Subunit
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Dr. Koji Ochiai Dr. Sankar Kuppusamy Yusuke Yasui Tsubasa Okano Yasunobu Matsumoto Dr. Nishant R. Gupta Dr. Yohei Takahashi Prof. Dr. Takaaki Kubota Prof. Dr. Jun'ichi Kobayashi Prof. Dr. Yujiro Hayashi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(10):3282-3286
Amphidinolide N, the structure of which has been recently revised, is a 26‐membered macrolide featuring allyl epoxide and tetrahydropyran moieties with 13 chiral centers. Due to its challenging structure and extraordinary potent cytotoxicity, amphidinolide N is a highly attractive target of total synthesis. During our total synthesis studies of the 7,10‐epimer of the proposed structure of amphidinolide N, we have synthesized the C1–C13 subunit enantio‐ and diastereoselectively. Key reactions include an l ‐proline catalyzed enantioselective intramolecular aldol reaction, Evans aldol reaction, Sharpless asymmetric epoxidation and Tamao–Fleming oxidation. To aid late‐stage manipulations, we also developed the 4‐(N‐benzyloxycarbonyl‐N‐methylamino)butyryl group as a novel ester protective group for the C9 alcohol. 相似文献
19.
The role of C? C bond‐forming reactions such as aldol condensation in the degradation of organic matter in natural environments is receiving a renewed interest because naturally occurring ions, ammonium ions, NH+4, and carbonate ions, CO32?, have recently been reported to catalyze these reactions. While the catalysis of aldol condensation by OH? has been widely studied, the catalytic properties of carbonate ions, CO32?, have been little studied, especially under environmental conditions. This work presents a study of the catalysis of the aldol condensation of acetaldehyde in aqueous solutions of sodium carbonate (0.1–50 mM) at T = 295 ± 2 K. By monitoring the absorbance of the main product, crotonaldehyde, instead of that of acetaldehyde, interferences from other reaction products and from side reactions, in particular a known Cannizzaro reaction, were avoided. The rate constant was found to be first order in acetaldehyde in the presence of both CO32? and OH?, suggesting that previous studies reporting a second order for this base‐catalyzed reaction were flawed. Comparisons between the rate constants in carbonate solutions and in sodium hydroxide solutions ([NaOH] = 0.3–50 mM) showed that, among the three bases present in carbonate solutions, CO32?, HCO3?, and OH?, OH? was the main catalyst for pH ≤ 11. CO32? became the main catalyst at higher pH, whereas the catalytic contribution of HCO3? was negligible over the range of conditions studied (pH 10.3–11.3). Carbonate‐catalyzed condensation reactions could contribute significantly to the degradation of organic matter in hyperalkaline natural environments (pH ≥ 11) and be at the origin of the macromolecular matter found in these environments. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 676–686, 2010 相似文献
20.
The aldol addition reaction of trichlorosilyl enol ethers and aldehydes with and without chiral Lewis base catalysts has been kinetically analyzed. The uncatalyzed reactions display classic first‐order dependence on each component. The reactions catalyzed by bulky chiral phosphoramide 5 were examined by ReactIR and exhibited first‐order dependence on the catalyst. To examine the kinetic behavior of the reaction catalyzed by phosphoramide 4 , a Rapid‐Injection (RI) NMR apparatus was constructed and employed to allow rapid in‐situ mixing and monitoring of the reaction course. The aldol addition catalyzed by 4 displayed second‐order dependence on phosphoramide, thus providing direct evidence that two catalyzed pathways (with complimentary stereochemical consequences) exist that depend on phosphoramide structure and concentration. Arrhenius activation parameters for all three reactions showed striking characteristics of negligible enthalpies and extremely high entropies of activation. Comparison of these values was precluded by the existence of complex preequilibria in the catalyzed process. 相似文献