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Search for "enzyme" in Full Text gives 542 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Navigating and expanding the roadmap of natural product genome mining tools
Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178
- the nascent NP rather than its chain extension, or utilized iteratively [22][23]. In textbook assembly line-like pathways, the architecture of the mega enzyme complex correlates with the product structure, a principle that is referred to as the colinearity rule [24]. Examples of these assembly line
- biosynthesis → polyketide biosynthesis). As such, NP biosynthetic pathways utilize members of existing enzyme families that have evolved to perform new metabolic functions. Consequently, NP BGCs “borrow” genes encoding paralogs of enzymes that have their origin in primary metabolism and that have diverged into
- catalyzing alternative metabolic functions. That way, the EvoMining approach identifies members of biosynthetic enzyme families that have likely been repurposed and thus, their corresponding genes are prime targets for a closer inspection of the genomic context to identify new types of BGCs. Although
Synthesis of (−)-halichonic acid and (−)-halichonic acid B
Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174
- (+)-2. If the biosyntheses of these natural products does occur through a common iminium ion intermediate, then our isolation of 11 suggests that the key aza-Prins cyclization is enzyme-mediated rather than spontaneous. Conclusion In summary, we have synthesized the enantiomers of halichonic acid and
Supramolecular approaches to mediate chemical reactivity
Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152
- reactants are confined in the restricted space provided by an enzyme binding pocket, the increase in local concentration, due to the proximity effect, the stabilization of intermediates and transition states cause the acceleration of the reaction. Thus, learning from natural enzymes, novel supramolecular
Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme
Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144
- fusicoccane-type diterpene synthases, in which a neutral intermediate is firstly formed and then protonated by an environmental proton. In addition, we demonstrate that the associated cytochrome P450 enzyme TadB is able to catalyze multiple oxidation of talaro-7,13-diene to yield talaro-6,13-dien-5,8-dione
- . Keywords: cytochrome P450 enzyme; diterpene synthase; gene cluster; genome mining; site-directed mutagenesis; Introduction Terpenoids are a large class of natural products that attract extensive attention, due to not only their potential applications in pharmaceuticals, agrochemicals, etc. but also due to
- Talaromyces wortmannii ATCC 26942, in which TadA is identified to be a new FC-type DTS responsible for the formation of talaro-7,13-diene, and the associated P450 enzyme TadB is characterized to be a multifunctional enzyme, converting talaro-7,13-diene to highly oxygenated talaro-6,13-dien-5,8-dione. Results
Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition
Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143
- enzyme PP2A [5][6]. Therefore, phoslactomycins [7][8][9][10][11][12] and leustroducsins [13][14][15][16][17] have been subject of extensive synthetic studies. In a project related to the synthesis of leustroducins and phoslactomycins, we have designed a convergent synthetic strategy involving the
Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase
Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142
- pathogen in these cases is mucoid Pseudomonas aeruginosa. Such infections are characterised by overproduction of the exopolysaccharide alginate. We present herein the design and chemoenzymatic synthesis of sugar nucleotide tools to probe a critical enzyme within alginate biosynthesis, GDP-mannose
- modifying C6 [4]. Substrate 18 was known to form a disulfide in solution [10], presumably resulting in the glycosyl-1-phosphate being unable to access the enzyme active site; unfortunately, the addition of higher concentrations of reducing agent (DTT) and solid-supported PPh3 to access the reduced form for
Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants
Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135
- four CYPs could produce stigmasterol from β-sitosterol (2) in enzyme assays performed in vitro. However, Arabidopsis CYP710A2 showed substrate flexibility towards campesterol (1) epimers and could also produce brassicasterol from 24-epicampesterol in vitro. Enzymes of the CYP51G subfamily (CYP51 clan
- our review provides a good starting point for such further studies. Enzyme function of cytochrome P450 monooxygenases (CYPs). A) Typical net reaction of CYPs, resulting in hydroxylation of a substrate. As monooxygenases, CYPs catalyse transfer of only one oxygen atom from molecular oxygen to their
Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions
Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134
- living organism investigated [1][2][3]. In 1956, Kornberg described the first polyP kinase (PPK) in Escherichia coli catalysing adenosine 5’-triphosphate (ATP)-dependent synthesis of polyP (Figure 2a) [4]. The enzyme was reclassified as family-1 PPK (PPK1) when a structurally different PPK (family-2
- model enzymes for PPK1 and PPK2 [9][10]. From a structure perspective, PPK1 enzymes form tetramers in solution with a mass of approximately 80 kDa for the monomer (Figure 2b). Although not being an integral membrane protein, the enzyme is described to be membrane-associated [11][12][13]. The phosphate
- transfer likely proceeds via formation of a phospho-enzyme intermediate (Figure 2d). Two essential histidine residues for autophosphorylation were identified by mutagenesis experiments [9][13][14]. Variants carrying mutations at these histidine residues lost the ability to synthesise polyP or ATP in vitro
Enzymes in biosynthesis
Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116
- proceed through multistep cationic cascade reactions and usually produce a polycyclic terpene hydrocarbon or alcohol with multiple stereogenic centers. While these transformations require only a single enzyme, polyketide and nonribosomal peptide biosyntheses are catalyzed by megasynthases that follow an
- assembly line logic, with individual domains for each single step [2]. Furthermore, the domains are organized into modules, each of which is responsible for the incorporation of one extender unit into the growing polyketide or peptide chain. With our knowledge today, the function of these large enzyme
- products, nature has evolved a large number of enzyme classes for more specific transformations, including cytochromes P450 or α-ketoglutarate-dependent dioxygenases for late-stage oxidations and transferases for the attachment of sugar units, acyl, or methyl groups. Moreover, some enzymes can catalyze
A Streptomyces P450 enzyme dimerizes isoflavones from plants
Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113
- challenging and often requires prefunctionalization of the substrate monomers, costly metal ligands, or tedious protection–deprotection steps [6][7][8][9]. With the advance of biosynthetic studies on natural products, a number of enzyme classes that are responsible for the dimer formation have been identified
- reactions (Figure S1, Supporting Information File 1). Due to the high reaction selectivity that the enzyme active site offers, these enzymes provide biocatalytic means for the biaryl linkage formation, and recent enzyme engineering efforts also demonstrated selective and efficient production of unnatural
- dimers or cross-coupling products, starting from simple monomers [17][18][19]. Nevertheless, our knowledge of enzyme-mediated dimerization is still limited in contrast to the numerous reported dimeric natural products. Phenol coupling in plant polyphenol biosynthesis is one of the earliest documented
New azodyrecins identified by a genome mining-directed reactivity-based screening
Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102
- enzyme VlmA [18]. This intermediate is hypothesized to be transformed into the azoxy bond-containing intermediate via an intramolecular rearrangement accompanied by a concomitant oxidation [18]. Although the exact mechanisms of azoxy bond formation remain unclear, VlmH and VlmA cooperate to biosynthesize
- the two-component flavin-dependent monooxygenase Ady3/Ady10, as in the valanimycin biosynthesis mediated by VlmH/VlmR [15][16][17]. The hydroxylamine would be conjugated to alanyl-tRNA to form an ester intermediate by the function of the tRNA-utilizing enzyme Ady7, which is homologous to VlmA. In
Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544
Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101
- ) HPLC analysis of the fermentation extracts of mutant S. sp. KIB-H1544-∆datA. (B) SDS-PAGE analysis of purified DatA (calculated molecular mass 101.8 kDa) and EchA (calculated molecular mass 105.4 kDa) protein. (C) HPLC analysis of in vitro enzyme reactions. Panel I, phenylpyruvic acid with boiled DatA
Understanding the competing pathways leading to hydropyrene and isoelisabethatriene
Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97
- . We show that there is a great thermodynamic preference for hydropyrene and hydropyrenol formation, and hence most likely in the synthesis of the isoelisabethatriene products kinetic control is at play. Keywords: diterpenes; enzyme mechanism; quantum mechanics; terpene synthases; thermodynamic and
- , having antibiotic and anti-inflammatory activities, respectively [4][5]. Unexpectedly, a single active site mutation, M75L, significantly shifts the product distribution and IE A becomes the dominant product (44%) in this enzyme variant [6]. As suggested by Rinkel et al., both routes (HP and IE routes
- isomerization is responsible for a slightly different substrate fold inside the active site, hence shifting the product distribution in favor of the IE products in certain enzyme variants rather than the HP products. Oxidation of IEs A and B by lipases results in the formation of the advanced pseudopterosin (P
Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa
Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91
- characterized the function of a P450 enzyme CYP76AH1 which was responsible for the formation of the aromatic ring of ferruginol in the biosynthesis pathway of tanshinones [34]. Hence, we proposed that the oxidation occurred on L to furnish the aromatic ring of calamenene (M) [29], followed by the hydroxylation
Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides
Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90
- -azaphospholidine-5-carboxylate 2-oxide (69) was sensible to glutaminase, an enzyme that could ring-open 1,2-azaphospholidine-5-carboxylate 2-oxides (Scheme 12) [32]. Griffiths and co-workers mentioned the synthesis of dimethyl (2-methoxy-1,3-dimethyl-2-oxido-1,3-dihydrobenzo[d][1,2]azaphosphol-3-yl)phosphonate (71
Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids
Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84
- characterization and analytical data; HDAC enzyme activity assay; references; NMR spectra. Acknowledgements The authors thank Mr. M. Malikenas for recording the HRMS. Results of the investigation were presented as part of a report on the 16th international conference of the Lithuanian Chemical Society “Chemistry
The stereochemical course of 2-methylisoborneol biosynthesis
Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82
- 2-methylisoborneol from (S)-2-Me-LPP may be explained by isomerization to 2-Me-GPP and then to (R)-2-Me-LPP. Keywords: biosynthesis; enantioselective synthesis; enzyme mechanisms; gas chromatography; terpenoids; Introduction After its first discovery from Streptomyces [1][2], it has been
- enriched 2-Me-LPP with 2-MIBS The enantiomerically enriched substrates (R)- and (S)-2-Me-LPP were incubated with purified 2MIBS (Figure S2 in Supporting Information File 1), followed by extraction of the enzyme reactions with hexane and GC/MS analysis of the obtained products (Figure S3, Table S1 in
- Supporting Information File 1). All compounds were identified from their EI mass spectra and retention indices in comparison to synthetic standards [29]. The substrate (R)-2-Me-LPP gave high yields of compound 1 (62% of total enzyme products in GC), besides 2-methylenebornane (10, 21%) and small amounts of 2
Synthesis of odorants in flow and their applications in perfumery
Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76
- min isoamyl acetate (10) is obtained in 59% yield according to GC analysis [26]. Related methods for the enzyme-catalyzed acetylation of isoamyl alcohol (9) have been developed utilizing biphasic systems, supercritical carbon dioxide as a solvent, or packed-bed reactors with immobilized enzymes [27
- esters with mainly fruity odor profiles are obtained in moderate to excellent yields. Some selected esters (14–16) and their odor profiles are shown in Scheme 4 [32]. Related methods for the esterification of natural occurring alcohols, such as geraniol, utilizing immobilized enzyme-catalysis in packed
- ) to (+)-nootkatone (8) under catalyst and solvent-free conditions in a segmented flow. Enzyme-catalyzed acetylation of isoamyl alcohol (9) in a biphasic n-heptane/water mixture utilizing a CorningTM Low Flow reactor. Esterification of alcohols by transesterification, catalyzed by immobilized
Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity
Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72
- -like acceptor compounds and farnesyl pyrophosphate (FPP) as most likely substrates for Ubi-297 (Maribacter sp. MS6). Thus, the 1st membrane faction containing membrane-bound UbiA-297 was subjected to an enzyme assay with farnesyl pyrophosphate (FPP) and different aromatic acceptor substrates in the
- the most favored substrate amongst the tested panel. Thus, we shortly investigated different reaction parameters using 8-HQA and FPP as substrates. First, we compared the enzyme activity of crude protein fractions directly obtained from cell lysate and enriched UbiA-297 fractions (Figure 6). As
- in pET28 vector (BioCAT GmbH) and transformed into E. coli BL21 for heterologous expression. Additionally, a modified ubiA-297(R145A) gene was synthesized and cloned into a pET28 vector (BioCAT GmbH) yielding pET28-297(R145A) for heterologous expression. Preparation of enzyme extracts and protein
Structural basis for endoperoxide-forming oxygenases
Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71
- endoperoxygenase NvfI. Keywords: biosynthesis; endoperoxide; enzyme; natural products; X-ray crystallography; Introduction Endoperoxide-containing compounds form a large group of natural products with cyclic peroxide structures [1][2][3][4][5]. These compounds are widely distributed in nature, and many
- cyclooxygenases, FtmOx1, and NvfI. Review COX: Heme-dependent cyclooxygenases in the biosynthesis of prostaglandins Enzyme reaction of COXs The cyclooxygenases are the best studied and understood oxygenases among the mammalian oxygenases [29][30]. Mammals have two cyclooxygenase isoforms, COX-1 and COX-2 [31][32
- are well conserved. While COX-1 is a constitutive enzyme present in most tissues, COX-2 is an isoenzyme induced in response to tumor promoters, growth factors, and cytokines [38][39][40]. Therefore, many COX-2 selective inhibitors are clinically used for treatments of inflammation, cancers, and pain
Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid
Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59
- for the aldolase from 108 to 42 mM and 91 to 37 mM, respectively. Keywords: aldolase; continuous fixed-bed reactor; enzyme; epimerase; GlcNAc; high pressure; immobilization; ManNAc; Neu5Ac; pyruvate; Introduction In times of a pandemic, the importance of substances to enhance the human immune system
- heparinus and the aldolase from Escherichia coli K12 were produced in E. coli BL21(DE3). Both enzymes were purified and immobilized on different carriers to find for each enzyme the best choice for a stable and active enzyme preparation when applied under high pressure in continuous operation. For screening
- purposes, six different carriers were used to immobilize the epimerase and aldolase (Table 1). The carriers differ in their properties (size, hydrophobicity, binding type, and porosity). The quality of immobilization was evaluated in terms of enzyme loading, activity, and reusability in repetitive batch
Terpenoids from Glechoma hederacea var. longituba and their biological activities
Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58
- spectrum of 1S,4S,5R,8S,10R-(1a). Finally, the ᴅ-glucopyranosyl moiety was identified by GC–MS analysis of a chiral derivatization product of the sugar obtained by enzyme hydrolysis of 1 [9][10]. The retention time of glucopyranose (11.3 min) corresponded to that of the standard ᴅ-glucopyranose (11.3 min
- 3C). The experimental ECD spectrum of 2 showed a negative Cotton effect at 233 nm and positive Cotton effects at 217 and 257 nm, which showed a similarity with those of calculated ECD spectrum of 1R,4R,5S,6S,8S,10S-(ent-2a). Enzyme hydrolysis and following sugar identification were performed using
- configuration of 3 was confirmed by comparing the calculated ECD spectrum of 3a (aglycone of 3) with the experimental ECD spectrum of 3. The experimental ECD of 3 displayed positive Cotton effects at 217 and 243 nm, which was similar to those of 1R,4R,5S,6S,10S-(3a) (Figure 4B). Enzyme hydrolysis and sugar
Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions
Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51
- ][10][11][12][13][14]. Among which, macrocyclic compounds have attracted extensive attentions due to their enzyme-mimicking cavity and preorganized binding sites [4][6][15][16]. Various macrocyclic compounds including the privileged scaffolds like cyclodextrins [17][18][19], calixarenes [20][21][22][23
Amamistatins isolated from Nocardia altamirensis
Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40
- +). This feature makes iron very useful as an enzyme cofactor for the shuffling of electrons. As a consequence of this, the transition metal is involved in many fundamental biological processes, such as respiration, photosynthesis, or nitrogen fixation [1]. In order to achieve iron homeostasis, organisms
A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions
Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38
- the active site of the enzyme. Once bound, substrate activation is carried out by specific amino acid side chains that adorn the inner surface of the cavity by means of a combination of covalent and/or weak intermolecular interactions leading to the stabilization of intermediate species and transition
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