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Search for "enzyme" in Full Text gives 553 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond
Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253
- offloading step always entails the same chemical reaction, wherein nucleophilic attack is promoted by the catalytic triad of a TE via general base catalysis. This is likely why traditional mechanistic studies that focused on the enzyme active site failed to work out how TEs control NRP topology. A priori
N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity
Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240
- mitochondria was changed. The presence of β-33b provoked a significant upregulation of the enzyme heme oxygenase-1. In conclusion, mitochondria are attacked by compound β-33b in the context of its cytotoxic activity against skin cancer cells. Aglycon 35 again proved to be inactive in all assays. It was
- mentioned above, that the free NH function of indirubin is important for CDK inhibition. We have shown in our group by enzyme studies that glycoside β-33b, lacking the free NH-function, does not act as a CDK inhibitor, despite its high activity against melanoma cells and other cancers [32]. These results
Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines
Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236
- this work was a preliminary evaluation of the potential bioactivity of the obtained compounds. In particular, a molecular docking experiment to investigate the binding mechanisms to the CYP51 enzyme and an evaluation of the antifungal activity of imidazo[1,2-a]pyrimidines against Candida albicans were
- -spectrum antifungal agents. Among the many drugs and hits, the azole-based systems (including triazoles and imidazoles) are of particular importance in this context. Their mechanism of action is the inhibition of the activity of the enzyme lanosterol 14α-demethylase (CYP51), which is encoded by the CYP51
- /ERG11 gene. This enzyme contains a haem-like prosthetic group in its active center and is a member of the cytochrome P450 family, which plays a key role in the biosynthesis of sterols. Sterols in turn are integral components of the fungal cell membrane, making inhibition of CYP51 [43] an effective
Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers
Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226
- fact, several inhibitors of the β-site amyloyd β A4 precursor protein cleaving enzyme (BACE1), which is involved in the production of β-amyloid, and fluoroalkene analogs of dipeptidyl peptidase-4 inhibitors have previously been reported [2][3]. These inhibitors possess higher drug efficacies than their
Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression
Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192
- nucleotides and amino acids, as well as energy molecules, salts, buffer, etc., are added. After successful protein synthesis, further substrates can be added for an enzyme activity assay. Although mimicking of cell-like conditions is an approach for optimization, the physical and chemical properties of CFPS
- osmolarity using ten different technical additives including organic solvents, polymers, and salts. It is shown that the synthesis of two model proteins, namely superfolder GFP (sfGFP) and the enzyme truncated human cyclic GMP-AMP synthase fused to sfGFP (thscGAS-sfGFP), is very robust against most of the
- biocatalysts [1][2]. The open environment allows easy manipulation of the protein synthesis [3] and coupling to subsequent enzyme activity assays, e.g., for substrate screening [4][5]. The CFPS system is advantageous for proteins that are difficult to express in a viable host cell, e.g., due to toxic effects
Natural resorcylic lactones derived from alternariol
Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187
- ring was isolated from Ulocladium botrytis [219] and Microsphaeropsis olivacea [167]. Its structure was unambiguously confirmed by NMR spectroscopy and by total syntheses [44][220]. Ulocladol is a tyrosine kinase (p56lck) inhibitor leading to a reduction of enzyme activity to 7% at 0.02 µg/µL) [219
Factors influencing the performance of organocatalysts immobilised on solid supports: A review
Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183
- ]. An advantage of dendrimer-supported organocatalysts are their enzyme-like properties [111][112]. Selective binding and cooperative catalysis can give the catalyst high selectivity and activity. Interactions between the support and other components The interaction between the solid support and the
Computational toolbox for the analysis of protein–glycan interactions
Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180
Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384
Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174
- μM. Compounds 1–5 were merely inhibitory against tyrosinase, showing 19, 13, 9.6, 18, and 15% inhibition at 200 μM, respectively, while a positive control, kojic acid, inhibited the same enzyme by 95%. Conclusion In summary, five new alkylpyrroles, allostreptopyrroles A–E (1–5), were discovered from
2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space
Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163
- tumor bed of a vast diversity of human tumor types. As phenylalanine is the preferred substrate of IL4I1 catalytic activity, Presset et al. [6] reported novel phenylalanine derivatives as a strategy to inhibit IL4I1 activity, as this enzyme has a preference for hydrophobic amino acids. Among them
The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)
Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162
- . 1.3 Compartmented and enzyme-mediated reactions Compartmentation of reaction media has already found many applications in chemistry. Amphiphilic molecules can associate in water to nanometer-sized micelles, above a certain critical concentration. Such micelles are characterized by a lipophilic core
- , respectively. For further investigations, however, CALB was chosen due to its lower cost and easier availability. Optimization of enzyme loading and substrate ratios increased the yield up to 91%. Immobilization of the enzyme on silica particles was not detrimental to the yield, but allowed enzyme recycling
- , obtaining an enzyme-metal biohybrid catalyst [22]. The authors tested it in a one-pot GBB reaction–Suzuki coupling, employing 5-bromo-2-aminopyridine (20), benzaldehyde (2), tert-butyl isocyanide (5) and phenylboronic acid (21). Compound 22 was obtained in 87% yield by performing the GBB reaction at room
A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts
Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161
- of applications in medicinal chemistry, chemosensors, polymers and catalysis [1][2][3][4][5][6][7][8]. Among them, flavins (Fl) are essential redox-active natural compounds that act as enzyme cofactors in numerous biochemical processes [9]. Structurally related to flavins are isomeric alloxazines
Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity
Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159
- its lanthipeptide precursor (Figure 2). A cluster analysis using BAGEL4 [4] confirmed the presence of terminators. The sequence information for CloA1 (precursor peptide), CloM1 (biosynthetic enzyme), CloPt1 (peptide domain), CloA2 (precursor peptide), CloM2 (biosynthetic enzyme), and CloPt2 (peptide
- the clostridial class (Figure S6 in Supporting Information File 1). Structure models for CloM1 and CloM2 generated using AlphaFold 2.0 (Figure S6B and S6C, Supporting Information File 1) were compared with the CylM [53] protein (PDB 5DZT), as it remains the sole LanM enzyme characterized through
- of 57u due to cysteine alkylation (Figure 4C and Table S8 in Supporting Information File 1). These analyses confirm the activity of the CloM2 enzyme, with the dehydratase domain activity forming a mixture of six and five times dehydrated lantipeptides, and the cyclase domain activity demonstrated by
Syntheses and medicinal chemistry of spiro heterocyclic steroids
Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152
- heterocyclic moieties containing three or more (hetero)cycles. Moreover, many compounds are accompanied by data on their biological activities, such as antiproliferative, antimalarial, antimicrobial, antifungal, steroid antagonist, and enzyme inhibition, among others, aimed at furnishing pertinent insights for
- polymeric version of 2-iodoxybenzoic acid (PS-IBX), was conducted to block the formation of the six-membered ring. Spiro-1,3-oxazolidinones 63 were assessed as inhibitors of 17β-HSD type 3, an enzyme involved in testosterone and dihydrotestosterone synthesis. The structure–activity relationship revealed
- that compounds bearing hydrophobic fragments were superior inhibitors compared to those with polar groups. Additionally, some derivatives exhibited better activity than the reference compound, with more than 40% inhibition of the enzyme. The research group also described additional spiro products
Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations
Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151
- using an enzyme or at what stage in a synthesis the enzyme is employed: 1) regio- and stereoselective late-stage functionalization of core scaffolds, 2) in situ generation of highly reactive intermediates, and 3) the one-step construction of macrocyclic or fused multicyclic scaffolds via regio- and
- I (9). As a pioneering investigation to elucidate the mechanism of this essentially identical allylic oxidations by Fe(II)/2OG-dependent dioxygenase, Dairi and co-workers conducted in vitro enzymatic conversions with the homologous enzyme Bsc9, derived from Alternaria brassicicola ATCC96836 [24
- ]. The P450 enzyme BscF is responsible for regioselective abstraction of a hydrogen at C12 and subsequent diastereoselective hydroxylation of the radical intermediate B to produce brassicicene B (10). Meanwhile, further single-electron oxidation of the intermediate B would trigger a Wagner–Meerwein-type
Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry
Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147
- can also be employed to mimic non-ribosomal peptides [12][13], since it is substantially more challenging to engineer non-ribosomal peptide synthetase (NRPS) pathways. Non-ribosomal peptides are often produced by giant multi-modular enzyme complexes (type I NRPS) and they are most commonly involved in
- remethylated to ʟ-methionine by the enzyme methionine synthase, which utilises 5-methyltetrahydrolate (5-MTHF) as a methyl donor. 5-MTHF is a constituent of the folate cycle, which encompasses the intermediates tetrahydrofolate (THF) and 5,10-methylene-THF (5,10-CH2-THF). 5,10-CH2-THF is formed from THF and ʟ
- atom, describing O-, N-, C-, and S-MTs; halide MTs have not (yet) been identified in RiPP pathways. The enzymes described below are either conventional SAM-dependent MTs or radical SAM (rSAM) MTs; rSAM MTs are one subfamily of the large rSAM enzyme superfamily, which encompasses enzymes catalysing a
Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty
Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146
- enzyme RagaA7 was produced in a Bacillus subtilis host and characterized to be a neoagarotetraose-producing GH-16 family endo-type β-agarase with a pH and temperature optima being 7.0 and 50 °C, respectively. Another thermostable neoagarotetraose-producing GH-16 endo-type β-agarase rAgaA was identified
- and cloned from deep-sea-derived Microbulbifer sp. JAMB-A94 with pH and temperature optima being 7.0 and 55 °C, respectively [26]. The recombinant enzyme was likewise produced using a B. subtilis host. The crystal structure of the catalytic domain was determined to show a β-jelly roll fold with
- 8.0 and 55 °C, respectively. The biocatalytic utility of the enzyme was also evaluated; it was used for neoagarooligosaccharide production in high yield [80]. Five additional GH-16 agarases AgaA3 produced in B. subtilis, ID2563 produced in E. coli, N3-1 produced in Pichia pastoris, AG1 produced in E
Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain
Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131
- : bioinformatics; conserved motifs; ketoreductase; polyketide synthase; stereocontrol; Introduction Type I modular polyketide synthases (PKSs) are large enzyme complexes that play a crucial role in the biosynthesis of bacterial polyketides, including many important clinical drugs such as erythromycin (antibiotic
- reside at the interface of domain–domain or domain–substrate interactions, shedding light on the enzyme mechanism for stereocontrol. Our work provides an overview for current bioinformatic prediction of stereoselectivity of KR in cis-AT PKS, expands the understanding of the stereocontrol of PKS from
Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis
Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102
- quinone structure. Consequently, we redirected our focus towards alternative, more electron-rich substrates. In a preceding investigation, we identified that the bifunctional enzyme JadH proficiently converted prejadomycin (9) to 8, a compound demonstrated to spontaneously oxidize to 1 under aerobic
- , compounds 4 and 5 were detected, and notably, a small amount of 10 was also observed (Figure 1, trace e). As expected, in the negative control reactions, 8 was spontaneously oxidized to 1 without any enzyme added, and no 4, 5, or 10 was observed; 1 remained unchanged in the reaction mixture with Fre, NADH
- the cofactor-independent enzyme NMO, employing dithranol as the substrate, unveiled the presence of a dithranyl radical and superoxide anion pair [29]. The production of the superoxide anion was captured using 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) and quantified by detecting
Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol
Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101
- stereochemistry. Theory is an important tool in understanding the complex chemistry in terpene synthesis. Gas-phase and in-enzyme tools have been employed extensively to understand terpene chemistry in general and terpene synthases in particular [21][22][23][24][25][26][27][28][29]. In the current work, we
- formation of (6,6) vs (5,7) is rooted in very slight changes in mechanism (protonation at C1 vs C10), it is of interest to understand whether there is a systematic difference in energy. In cases where enzymes use pathways with high-energy intermediates, the enzyme active site must in some way direct the
Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A
Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96
- development of more potent CDA and APOBEC3 inhibitors. Keywords: APOBEC3; cytidine deaminase; enzyme activity; inhibitor; nucleoside; nucleotide; zebularine; Introduction Spontaneous hydrolytic deamination of cytosine to uracil (Figure 1A) is very slow under ambient conditions [1], but it is greatly
- bacteria and fungi but not in mammalian cells, acts only on cytosine. Cytidine deaminase (CDA) as a key enzyme in the pyrimidine salvage pathway in mammals deaminates both cytidine and 2'-deoxycytidine. Members of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family, such as
- (MDS) and chronic myelomonocytic leukaemia (CMML) [8]. In normal human cells, the enzyme family A3 [9][10][11][12] disables pathogens by scrambling ssDNA by cytosine to uracil mutation (Figure 1A) [9][10][13][14]. However, several enzymes, particularly A3A, A3B, A3H and A3G, deaminate cytosine in human
Enhancing structural diversity of terpenoids by multisubstrate terpene synthases
Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86
- enzymes (Table 1) [18]. A TPS-f subfamily enzyme CoTPS5 from Cananga odorata has been characterized to convert 3 to (E)-β-ocimene (9), 4 to 8, and 5 to diterpene α-springene (10) (Figure 2) [22]. Both in vitro assays and in vivo transgenic expression of CoTPS5 confirmed the absence of side products
- TSs and three PTs to generate 4, 5 or geranylfarnesyl diphosphate (GFPP, 29, Figure 1), representative products 30–33 are shown in Figure 3a [28]. Notably, FgMS is a chimeric enzyme (PTTS) consisting of an N-terminal class I TS domain and a C-terminal GFPP synthase domain. Therefore, to block the
Synthesis and properties of 6-alkynyl-5-aryluracils
Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80
- a targeted enzyme [21][22][23]. One of these focus areas was the synthesis of alkyne-linked derivatives. The first alkyne-linked compound was already published in 1976, accompanied by new synthesis methods in the following years [24][25][26][27]. With the discovery of potential antiviral properties
Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria
Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75
- antibiotic activity towards Gram-negative bacteria. An NNG degrading heme enzyme, called NnlA, has recently been discovered in the genome of Variovorax sp. strain JS1663 (Vs NnlA). Evidence is presented that NnlA and therefore, NNG degradation activity is widespread. To achieve this objective, we
- NnlA cannot degrade the NNG analog 2-nitroaminoethanol. The combined data strongly suggest that NnlA enzymes specifically degrade NNG and are found in diverse bacteria and environments. These results imply that NNG is also produced in diverse environments and NnlA may act as a detoxification enzyme to
- nitramine. An enzyme, N-nitroglycine lyase A (NnlA), from the bacterium Variovorax sp. strain JS1663 (Vs NnlA) was recently shown to degrade NNG. This strain was enriched from sludge from the Holston Army Ammunition Plant using selective growth media containing NNG as the only carbon and nitrogen source [20
Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus
Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73
- calidoustene C, DrtB from Aspergillus calidoustus functions as a dual-functional enzyme, comprising two domains: a HAD-like hydrolase domain fused with a terpene cyclase domain. Initially, FPP is cyclized into the drimenyl diphosphate in a class II terpene cyclase manner, which is then processed by the
- with literature data [29]. This marks the first discovery of natural DMTs from bacteria, surpassing previous findings of bacterial DMSs which focused only on the enzyme itself without reporting natural DMT or exploring associated BGCs [17]. Additionally, while drimentines, bacterial meroterpenoids
- utilizing the EFI-genome neighborhood tool (EFI-GNT), sequence alignment, and manual BLAST analysis [33]. Leveraging our previous discovery of SsDMS from Streptomyces showdoensis, we identified a homologous terpene cyclase (sclav_p0068) in S. clavuligerus. This enzyme shares a 50% sequence similarity with
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