Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• duplication events during genome evolution [96]. When expressed in the callus of Nicotiana tabacum, GjCCD4a exhibited a higher efficiency in carotenoid cleavage than CsCCD4a [85]. ALDHs: ALDH utilizes NAD+ or NADP+ as cofactor to catalyze the oxidation of acetaldehyde into carboxylic acids. In 2018, Demurtas

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• is a myo-inositol dehydrogenase. These types of enzymes typically use NAD+ as a cofactor [12][13]. So, we first tested Hyg17 with myo-inositol and NAD+ and found that it was able to produce NADH, suggesting it can function as a myo-inositol dehydrogenase (Figure 2a). Since this assay tests for the

• formation of NADH, we are assuming the formation of a ketone product. However, further experiments are required to verify this assumption and determine which inositol position is being oxidized. When we tested Hyg17 with myo-inositol and NADP, we found no activity, showing that Hyg17 is NAD+-dependent

• (Figure 2b). Although this is consistent with native myo- and scyllo-dehydrogenases LcIDH1 and LcIDH2 from Lactobacillus casei [12], there have been reports of a genetically engineered NAD-specific dehydrogenase that has been converted to an efficient NADP-dependent enzyme [14]. Next, we determined the

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• NAD(P)-dependent oxidoreductase, suggesting that the denitrification activity of AvaA7 is not an artifact and that AvaA7-catalyzed denitrification is a genuine reaction in bacterial cells (Figure S6 in Supporting Information File 1 and Table 2). Discussion In the present study, we showed that the cma

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• in a suspension or solution, that an impurity in the enzyme suspension or solution does not interfere with the measurement. Thus, when a spectroscopic method is used for an equilibrium measurement (e.g., in an NAD/NADH coupled reaction), it has been customary to perform a control experiment in which

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• = red, phosphorus = purple, chlorine = green, hydrogen = pink. C6–Cl is the gg rotamer (from the Cl6–C6–C5–O5 torsion angle). GMD function with probe 19 over 120 min (GMD (100 µg/mL), GDP sugars (50 µM), NAD+ (200 µM)). Dotted trace dictates expected fluorescence output following spiking with GDP-Man 1

Enzymes in biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116

• , requiring a sophisticated enzymology [4]. Recent developments show us that there is still much more to discover, e.g., altemicidin was shown to be enzymatically constructed from NAD+ and SAM that usually serve as enzyme cosubstrates in redox transformations and methylations but are rarely used to construct

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• S. sp. KIB-H1544, we conducted the following experiments. Firstly, the genome of S. sp. KIB-H1544 was sequenced, and bioinformatic analysis yields the three-genes cluster (NCBI accession number: ON973849) encoded by datA (peptide synthetase), datB (NAD-dependent dehydratase), and datC (limonene-1,2

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• their catalytic site, while the remaining 7 isoforms of class III, known as sirtuins, are dependent on the NAD+ coenzyme [3][4]. According to current knowledge, HDAC inhibitors usually have several structural subunits: a zinc chelating group, a hydrophobic linker, and a hydrophobic (usually aromatic

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• mM ManNAc, 2 mM NAD, and 0.05 mL ManDH solution with 3 kU/mL. After starting the reaction, the mixture was incubated at room temperature for 30 minutes. The resulting NADH concentration was measured with an Eppendorf spectrophotometer at 340 nm. High-pressure set-up An HPLC pump (Nexera X2 LC-30AD

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• , followed by oxidation, thus establishing a redox cycle. The main characteristics of the quinones (Q) redox cycle, comprises the one-electron reduction to generate a semiquinone intermediate (SQ) and the two-electron reduction leading to hydroquinone (HQ), in NAD(P)H oxidase-dependent processes [35][36][37

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• simulated with concentrations of D (NAD(P)H) and Q (NAD(P)+) constant throughout the reaction. This is a fair approximation for what happens with efficient recycling. Figure 1 shows the simulated progress of a reaction for a set of plausible conditions and enzyme properties. In all cases the product ee

• more efficient process, but the result may be an undesirable fall in ee at higher conversions. Reaction progress for “ordered, second” kinetics and the effect of D/Q (e.g., NADH/NAD+) ratio. S0 = 0.2 M, total D + Q = 0.01 M, Keq = 5, E = 39, KMD = 0.001 M, KMS = 0.001 M, k4 = 1000 s−1, SCRf/b = 1, k3R

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• for illustration is the heterodimer of human NAD-dependent isocitrate dehydrogenase (Protein Database (PDB): 6KDF) [10]. Figure adapted from Carter et al. [11]. Mechanisms of homooligomeric complex formations. a) Domain swapping of RNase A (PDB: 1A2W) [73]. The swapped regions are shown in red. b

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• mostly chemically indistinguishable, while many P450s are known to selectively act on specific carbon atom(s). A continuous electron input is required to keep CYPs functional [83]. In general, soluble bacterial CYPs utilize class I redox systems, where the electron from NAD(P)H is delivered to CYPs

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• aryl substituent located on the nitrogen atom. Nucleotide pyrophosphatase activity Nucleotide pyrophosphatases belong to the family of ecto-nucleotidases [34][35]. They can hydrolyze nucleotides, dinucleotides, and nucleotide sugars, e.g., ATP, ADP, NAD+, ADP-ribose and diadenosine polyphosphates [36

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• ). In 2007, Schmid explored the application of Rh complex 141 as a mediator for NADPH recycling [80]. This report showed that asymmetric electroreduction of cyclohexanone 140 in organic/aqueous media can be efficiently catalyzed by thermophilic NAD-dependent alcohol dehydrogenase (TADH) and result in

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• . This class of lysine deacetylases (KDACs) is distinguished from others by their dependence on the cosubstrate NAD+. In mammals, seven sirtuin isoforms have been identified to date [1]. These can be grouped into five classes (I, II, III, IV and V) according to their phylogenetic relationship [2]. The

• studies proposed a binding mode in which 2a mimics the nicotinamide residue of NAD+, whereas aromatic amino acid residues of the selectivity pocket stabilize the dimethylphenol ring [35]. As photoisomerization in stilbenes and azo dyes is accompanied by a perpendicular twist of the phenyl ring towards the

• −356, and Sirt3118−395 was carried out as described previously. Identity and purity were verified by SDS-PAGE [65]. Protein concentration was determined by the Bradford assay [66]. Deacylase activity of sirtuin isotypes could be inhibited with nicotinamide and was shown to be NAD+-dependent. Bioassay

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• reviewed in this article. Syntheses were clustered based on: i) syntheses using tetralone (Figure 2, route A nad B), ʟ-abietic acid and/or ʟ-dehydroabietic acid as starting materials (route C, D and E); ii) syntheses using Diels–Alder reactions for the construction the A, B and C-rings (route F and G); iii

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• Mikhail V. Makarov Marie E. Migaud Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Ave., Mobile, AL 36604, USA 10.3762/bjoc.15.36 Abstract The β-anomeric form of nicotinamide riboside (NR+) is a precursor for nicotinamide adenine dinucleotide (NAD+), a redox cofactor

• nicotinamide adenine dinucleotide (NAD+, Figure 1), an intracellular redox cofactor, central to all cells’ biochemistry. Unlike its phosphorylated and reduced forms, NAD+ is also a non-redox substrate for many intra- and extracellular enzymes, participating in cellular signaling pathways and regulating post

• -translational protein modification events [1][2][3]. During the process of aging and in several disease models, the demand on the NAD+ pool far exceeds its availability [4][5][6]. While nicotinic acid [7] and nicotinamide [8][9] are long-standing vitamin B3 supplements known to restore depleted NAD+ levels [10

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• products [4], medicines [5], chelating agents in transition metal complexes [6][7], and material science [8][9]. Pyridine derivatives such as vitamins B6, B3 (niacin), and nicotinamide adenine dinucleotide (NAD) play a significant role in the metabolism process of living organisms. Consequently, many

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• sequence of the protein is closer to that of P. putida S16 NicA2 than LHNO from A. nicotinovorans. VppD is an NAD(P)-dependent flavin monooxygenase whose sequence is 62% identical to that of P. putida S16 HspB. The crude recombinant VppE catalyzes the iron-dependent oxidation of 2,5-dihydroxypyridine to N

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• adenosine-5′-monophosphoromorpholidate with the sodium salts of 5′-phosphorylated nucleosides without any predrying and in the presence of acidic promoters and water gave complete reaction within 90 minutes (Scheme 13) [53]. In this original report, the preparation of nicotinamide adenine dinucleotide (NAD

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• selective oxidation of trans-hex-2-enol. A: Alcohol dehydrogenase (ADH)-catalysed oxidation producing stoichiometric amounts of NAD(P)H, which needs to be recycled in situ; the overall reaction is reversible requiring surpluses of the cosubstrate (e.g., acetone) to shift the overall equilibrium to the side

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• enzymes belong to the family of oxidoreductases with NAD+ or NADP+ as electron acceptor. This oxidation is a mandatory step for removing the OH functionality at C12. In all the chemoenzymatic routes reported by Eggert et al. [20], the carbonyl group resulting from the oxidation of the 12-OH group was

• leptum [48] and Clostridium group P strain C 48–50 [49][52]). Furthermore, on the other side, the NAD+-dependent 12α-HSDHs activity was observed and reported in Eubacterium lentum and Clostridium perfringens [50][51]. A NAD+ dependent process for the production of 12-oxo-CDCA was patented in 2006 [53

• presented in the next paragraphs. 7α-Hydroxysteroid dehydrogenases (7α-HSDH) These enzymes are able to oxidise specifically the α-hydroxy group at C7 together with the concomitant reduction of NAD+ or NADP+ (Figure 5). All of them are part of the group of the short chain dehydrogenases/reductases (SDR

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• ], NAD-capped RNAs [23][24], 3'-dephospho-CoA linked RNA [25] or methylphosphate capping [26][27] we refer to the indicated articles. Review Enzymatic preparation of capped mRNA Enzymatic preparation of capped mRNA is based on in vitro transcription (IVT) of a DNA template. While RNA synthesized via

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• nucleophile (Figure 6) [54]. Rarer mechanisms have also been discovered, like for example the one of i) myrosinases in plants that are retaining GHs that lack a general acid and use an exogenous base [55], or ii) some GHs from families 4 and 109 which follow a NAD-dependent hydrolysis [56][57]. Even if the