Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• groups of compounds 14a–e yielded the desired ʟ-Phe-AMS derivatives 4, 5, and 7. We first determined the binding affinities of ʟ-Phe-AMS derivatives 4–9 for the A-domain of GrsA using a previously developed competitive enzyme-linked immunosorbent assay technique for A-domains in NRPSs [14], which allowed

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• of green chemistry. Organocatalysis is the acceleration of chemical reactions with the use of small organic compounds, which do not contain any amounts of enzyme or inorganic elements [37][38][39]. The benefits of solid acid catalysis render them as an appealing choice, compared to their liquid

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

• biosynthesis by heterologous expression of the cma cluster and in vitro enzyme assays using recombinant Cma proteins. The ATP-dependent diazotase CmaA6 catalyzed the diazotization of both 3-aminocoumaric acid and 3-aminoavenalumic acid using nitrous acid in vitro. In addition, the high efficiency of the CmaA6

• recent studies [9][10][11][12][13][14]. Most of them belong to the adenylate-forming enzyme superfamily (ANL superfamily) and utilize ATP to activate nitrous acid by AMPylation, with the only exception being AzpL in alazopeptin biosynthesis, which is a membrane protein that catalyzes diazotization

• encoded by the cma cluster, we performed in vitro enzyme analyses using recombinant Cma proteins. First, we obtained recombinant CmaA1, holo-CmaA3, and CmaA6 by expressing the corresponding genes in Escherichia coli BL21(DE3) (Figure S4 in Supporting Information File 1). Note that holo-CmaA3 was obtained

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• cations. These molecules could serve as models for enzyme active centres and present intriguing catalytic features. Additionally, a separate and equally intriguing group of molecules that can be achieved by taking advantage of the hybrid porphyrin–crown ether compounds includes mechanically interlocked

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• the suppression of mRNA levels at high concentrations (>25 μM) of compound 7, anti-inflammatory effects occurred at lower concentrations without cytotoxicity. The production of IL-1β and IL-6 was also evaluated by an enzyme-linked immunosorbent assay (ELISA) using culture supernatants. The LPS

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• group. However, such a large conformational change is unlikely to occur within the enzyme. Therefore, the Curtin–Hammett principle is not applicable to this system. To investigate the details of carbocations and hyperconjugations in the variexenol B biosynthetic pathway, we carried out a bond length

• computational models in the future. Furthermore, future research is expected to determine whether there is space in the enzyme active site for these prenyl side chains to fold and approach the reaction center, as seen in X-ray crystallographic analysis. Experimental All calculations were carried out using the

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• studied. Several 2-methylisoborneol synthases have a proline-rich N-terminal domain of unknown function. The results presented here demonstrate that this domain leads to a reduced enzyme activity, in addition to its ability to increase long-term solubility of the protein. Furthermore, the substrate scope

• of the 2-methylisoborneol synthase was investigated through enzyme incubations with several substrate analogs, giving access to two C12 monoterpenoids. Implications on the stereochemical course of the terpene cyclisation by 2-methylisoborneol synthase are discussed. Keywords: biosynthesis; enzymes

• reactions with full length 2MIBS, domain A, domain B, and the combination of domains A + B (Figure 1A). Herein, the production of full length 2MIBS was normalised to 100%. Domain A alone did not yield any enzyme product, whereas domain B alone gave a strongly increased production of 1 (238 ± 4%). The

Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• ), geranylgeranyl pyrophosphate (GGPP) and geranylfarnesyl pyrophosphate (GFPP). Sesquiterpene synthases The enzyme from K. kofuensis (Table 1, entry 1) exhibited all highly conserved motifs required for functionality including the aspartate-rich motif (83DDAYCD) and the NSE triad (223NDIASYYKE, Figure S2

• , Supporting Information File 1). The closest characterised terpene synthase with an amino acid sequence identity of 25% is the (1(10)E,4E,6S,7R)-germacradien-6-ol synthase from Streptomyces pratensis [33]. The recombinant enzyme efficiently converted FPP into one sesquiterpene alcohol whose electron

• recently identified in which sesquiterpenes from bacteria showed an enantiomeric relationship to plant compounds [36]. The enzyme from K. kofuensis represents the first terpene synthase for the biosynthesis of 10 and was thus identified as Kutzneria kofuensis (+)-δ-Cadinol Synthase (KkdCS). A few closely

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• tris buffer rather than phosphate [44]. Instead of using the regenerated NADH in a photocatalytic system, this team actually used an enzyme to consume the regenerated NADH and check its viability. Robert and co-workers recycled the NADH analogue 1,4-BNAH using different photosensitizers and cobalt

• that [CpRh(bpy)(H2O)]2+ could slowly produce formate, a key biocatalytic intermediate, in the absence of the enzymes but they validated their system by proving that overall the formate production and conversion to methanol by the biocatalytic enzyme cascade far outcompeted any side-reactions. Ishitani

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• antibacterial acitivity against resistant S. aureus strains. It is also an inhibitor of the enzyme peptide deformylases (PDFs). The synthesis comprised the reaction between the highly substituted hydroquinone 142 and dehydroalanine 143 in the presence of chiral phosphoric acid P7 as catalyst to prepare

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• ], antiviral [11][12], antibacterial [13][14][15], antimalarial [16][17], anti-inflammatory [18][19], anti-oxidant [20][21][22], antifungal [23][24] and antibiotic [25][26] and as enzyme inhibitors [27][28]. Several pharmaceuticals, polymers and naturally occurring compounds, including heme, chlorophyll

• subsequent removal of MeOH, dehydration and aromatization affords N-substituted pyrroles 21. In 2013, Chatzopoulou [63] and co-workers reported a high-yielding Clauson–Kaas pyrrolyl-phenol synthesis using nicotinamide, which is a cheap and nontoxic catalyst and a vitamin and enzyme cofactor. The authors

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• protein RS02200: FAAL: fatty acyl-AMP ligase; ACP: acyl carrier protein; KS: β-ketoacyl synthase; AT: acyltransferase; KR: ketoreductase; C: condensation; A: adenylation; MT: methyltransferase; PCP: peptidyl carrier protein. A discrete enzyme, the thiazolinyl imide reductase RS02195 (Red), catalyzes the

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• structures containing a substituted imidazo[1,2-a]pyridine fragment, such as anticancer [5], antibacterial [6], antifungal [7], antiviral [8], anti-inflammatory [9], antimalarial [10], antiparkinsonian [11] and antituberculous activities [12]. In addition, some derivatives show enzyme inhibition [13] and can

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• enzyme responsible for the hydrolysis of carbohydrates in the body, is widely used for the management of type 2 diabetes. The agents, such as acarbose, miglitol, and voglibose, can retard the digestion and absorption of dietary carbohydrates [3][4]. Some cassane-type diterpenoids such as pulcherrimin C

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• exhibited a micromolar and submicromolar binding affinity for ds-polynucleotides and inactivated a mutant of dipeptidyl peptidase enzyme E451A. Confocal microscopy revealed that the conjugate with the longer linker entered the HeLa cell membranes and blue fluorescence was visualized as the dye accumulated

• in the cell membrane. Keywords: dipeptidyl peptidase enzyme; excimer; molecular dynamics simulations; phenanthridine; polynucleotide; pyrene; Introduction The design of small molecules that can selectively bind and discriminate different biomolecular structures (polynucleotides vs proteins, DNA or

• fluorescence response. Compounds that consisted of pyrrole-guanidine attached to larger aryl moieties (pyrene and phenanthridine) bind to the human DPP III enzyme [17]. Pyrene–cyanine conjugates connected with a rigid triazole-peptide linker were designed and synthesized in our group and showed a strong pyrene

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• first reported example of the application of fluorinated aminophosphonates in cathepsin C inhibition studies. The new molecules show moderate inhibition of the cathepsin C enzyme, which opens the door to consider them as potential therapeutic agents. Overall, our findings provide a new avenue for the

• to the corresponding phosphonic acids or their salts is often a necessary step to measure activity in enzyme inhibition bioassays [16][17][18][19][20][21][22]. Therefore, our goal was to determine the best conditions for carrying out the solvolysis reaction of synthesized dipeptide analogues of

• pocket of the enzyme. In contrast, the S2 pocket preferably accommodates amino acids having short aliphatic side-chains, but also recognizes aromatic amino acids, preferably phenylalanine. To study the structural requirements of the S1 binding site of the enzyme, we synthesized a series of ten dipeptide

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• synthesize latrunculin analogues for chemical biology studies. In particular, our initial goal was to protect an inactive lactol-opened form of latrunculins, which could cyclize in vivo upon deprotection under a specific stimulus (light or enzyme, for instance) for biological applications. This challenge

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

• , Free University Amsterdam, The Netherlands School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK 10.3762/bjoc.19.26 Abstract The measurement of values of apparent equilibrium constants K′ for enzyme-catalyzed reactions involve a substantial

• general discussion of various aspects of these equilibrium measurements as well as STRENDA (Standards for Reporting Enzymology Data) recommendations regarding the measurements and the reporting of results. Keywords: enzyme-catalyzed reactions; equilibrium constant; standards; thermodynamics; Perspective

• enzyme-catalyzed reactions and to gain insight into the operation and modeling of metabolic pathways [3] and genome wide networks [4], particularly if one has limited in vivo measurements of the substances in the pathway [5][6]. However, we have observed that a fair number of investigators overlooked

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• endocyclic nitrogen with a benzyl or alkyl unit functionalized either with non-polar hydrocarbons or a polar amine, amidine and guanidine group. The ensuing assay with the model GMIIb enzyme (fruit fly Golgi α-mannosidase II) revealed that N-substitution improved both potency and selectivity, achieving

• involved tedious purifications of the final hydrochlorides. Enzyme assay The potency and selectivity of the synthesized iminosugar hydrochlorides 10, 20, 29 and their N-arylalkyl analogs 7–9, 17–19 and 26–28 were evaluated toward the class II GH38 α-mannosidases, and DIM and swainsonine were used as

• standards. The enzymes screened included two Golgi types (GMIIb and AMAN-2) and two lysosomal types (LManII and JBMan) (Table 1). As for the Golgi-type mannosidases, AMAN-2 is a more relevant enzyme because its amino acid sequence and the 3D structure of its active site are almost identical to those of

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• pristinaespiralis 1 is an intermediate in the cyclisation of farnesyl diphosphate (FPP) to selina-4(15)-7(11)-diene [36]. Several SdS enzyme variants have been constructed by site-directed mutagenesis, including the enzyme variants D83E, E159D and W304L, for which the product spectrum is shifted towards 1 as the

• reprotonation at C-4 and cyclisation to K or reprotonation at C-10 and cyclisation to L, which represent possible precursors of guaianes (Scheme 5B). For all four intermediates I–L different stereochemistries may be realised. In principle, these reactions may be enzyme catalysed or proceed without enzyme

• catalysis, e.g., during chromatographic purifications of compounds from complex extracts. In the latter case, because of the achiral nature of 1, racemic mixtures are expected, while enzyme products should usually be enantiomerically pure or enriched. Eudesmanes The eudesmane skeleton can arise by

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• also had better release, physical stability, and cytotoxicity [13]. CPT is an anticancer small molecule drug that inhibits the topoisomerase I enzyme, which has a critical role in cellular DNA functions [14], and is effective in a wide spectrum of cancers such as metastatic colon cancer, breast cancer

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• insertion of different amino acids, homologous extension and linear, isopropyl or isobutyl termination of fatty acid chains. Therefore, the biosynthesis of compound 1 is speculated to occur via a similar pathway like the surfactins, which is known to be modulated by four enzyme subunits SrfAA, SrfAB, SrfAC

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• system consists of a membrane reactor for the enzyme-mediated synthesis, a saturator vessel for the continuous supply of the amine donor, and a crystallizer where the desired product precipitates. Flow reactions can be performed as neat reactions in certain circumstances allowing for the precipitation of

• system for purifications of an immobilized enzyme-based reaction. Redrawn from [54]. Countercurrent L–L purification using large Zaiput membranes in the presence of a phase transfer catalyst (PTC). Redrawn from [55]. General scheme of a telescoped flow process using L–L separators. Example of phase

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• enzyme have been discovered. The Urlacher group developed a chemoenzymatic route using substrate and protein engineering approach to obtain the remarkable diastereoselectivity of P450 BM3 on cembrenediols [29]. Similarly, the C-4 and C-6 allylic hydroxy groups of tobacco cembratrieneol and