Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• with residual organic waste streams, such as milling or forestry waste. Additionally, the heterologous terpene production minimizes waste generation as the targeted production of a single compound reduces extraction and purification steps [24][25]. Additionally, heterologous production enables protein

• conformation change of the G1/G2 helix kink, which is not observed in the structures of CotB2 [36][37][38]. This might be explained by the observation that the pyrophosphate sensor of CotB2 R177 and D180 is already involved in a salt bridge in the open conformation. The WXXXXXRY motif Analyzing protein

• dogmatic dispute in the TPS community about the respective roles of the protein acting as a scaffold and the “inherent” carbocation reactivity [91] in orchestrating an enzyme specific reaction cascade. With regard to the latter, the “inherent reactivity” of carbocations is no doubt an important ingredient

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

• ‐time photomodulation of sirtuins in vitro. Keywords: azo compounds; epigenetics; photoswitch; sirtuins; stilbenes; Introduction Sirtuins are protein deacylases that cleave off not only acetyl, but also other acyl groups from the ε-amino group of lysines in histones and many other substrate proteins

• −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

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• prediction of the potential terpene synthases in J1-030 genome, gene Tvi09626 was selected and the following bioinformatics analysis of the function of this unidentified terpene synthase was performed. A protein blast search against the NCBI database was performed with Tvi09626, revealing sequence identities

• construct the plasmid pXS222. Next, pXS222 was transformed into BL21 to overexpress and purify Tvi09626 (Figure S2, Supporting Information File 1). The substrates GPP, FPP and GGPP were incubated with the protein individually and the products were detected and analysed by gas chromatography/mass

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• effects on cells infected with respiratory syncytial virus [22][23], induction of aerial mycelium formation in Fusarium culmorum [24], and as an inhibitor of ubiquinol-cytochrome c reductase binding protein, blocking mitochondrial ROS-mediated vascular endothelial growth factor receptor type 2 signalling

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

• pathways involved in the regulation of reactive oxygen species (ROS) and/or nitric oxide (NO) [9], histone methyltransferase [10], HSP70 [11], Jak2, Bcl-2/Bax [12], caspase 8 [13], NF-κB [14], X-linked inhibitor of apoptosis protein (XIAP) [15], MAPK, PI3K [16], and MPK1, ERK-1/2, and JNK-1/2 [17]. The

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• well. It should be specially emphasized that 2-diarylmethyl and 2-arylmethyl-substituted benzimidazoles 9–12 are synthetically hardly available compounds [27][28]. For instance, they were investigated as AMP-activated protein kinase activators [27]. Conclusion Reactions of 2-carbonyl and 2-hydroxy(or

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• that this SL does not act as SERCA inhibitor. Therefore, we proceeded to confirm this hypothesis by a molecular dynamics simulation study. Molecular dynamics simulation of compounds 1 and 2 with SERCA The binding cavity for thapsigargin and compound 2 in the SERCA protein lies in the transmembrane

• 1); ii) compound 1 rotated by 180° (simulation 2); iii) compound 2 (for comparison) used as a ligand with the orientation equal to DTB (simulation 3); iv) SERCA positioned in a phospholipid membrane to reflect the fact that it is a transmembrane protein, with compound 2 as a ligand (simulation 4

• parts of Glu255 and Gln259 were detected. When the simulation was performed without constrained positions, compound 1 escaped from the SERCA protein cavity. After the first simulation of compound 2 (simulation 3) in non-water environment, hydrogen bonds of compound 2 with Glu255 and Gln259 residues, and

Complexation of chiral amines by resorcin[4]arene sulfonic acids in polar media – circular dichroism and diffusion studies of chirality transfer and solvent dependence

• Bartosz Setner and
• Agnieszka Szumna

Beilstein J. Org. Chem. 2019, 15, 1913–1924, doi:10.3762/bjoc.15.187

• protein crystallizations. Due to the interest in interactions with proteins we have selected basic amino acids as chiral bidentate amines to interact with RSAs. We have also studied interactions of RSAs with chiral tetradentate ligands (tetraaminocavitands) in order to evaluate the influence of a chelate

• sensitive technique for the detection of noncovalent interactions involving chiral molecules, even if only one component of the interaction pair is chiral. Considering strong interactions with amino acids we think that RSAs, in analogy to CSAs, can also act as modulators of protein crystallizations

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• ][15][16][17][18][19]. Among all the developed S(VI)–F species, sulfonyl fluoride (RSO2F) was specifically recognized as unique scaffold for covalent protein inhibitors and biological probes with the affinity-driven activation for forming covalent linkages with the amino acid residues of protein

• coupling reactions and as potential covalent probes in protein profiling [14][25][26][27][28]. Phenols (or alcohols) and amines as the most common nucleophiles have been found to react with different S(VI) connectors (SO2F2, CH2=CH-SO2F, SOF4 etc.) to provide diversified sulfonyl fluoride derivatives. The

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• can sometimes bind to the active site in an unreactive conformation [11]. Recently, Siegel and Tantillo reported an innovative method for predicting the docking mode of carbocation intermediates in terpene cyclase [12][13], based on QM calculation and computational docking with the Rosetta protein

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• common feature of mono- and distyryl dyes, including long-known mono-styryl dyes used as mitochondrial probes or protein stains. However, the magnitude of the G4-induced “light-up” effect varies drastically, as a function of both the molecular structure of the dyes and the nature or topology of G4

• initially developed for detection or visualization of DNA, RNA, or other analytes, either in vitro or in cellular imaging applications, must be reassessed in view of their potential strong bias for G4 motifs. Indeed, a remarkable “light-up” effect of SYPRO Orange, a widely used protein stain belonging to

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• replacing the whole Mycobacterium in complete Freund’s adjuvant. MDP triggers an immune response by activating the mammalian NOD-like receptor, nucleotide binding oligomerization domain-containing protein 2 (NOD2). NOD2 is an intracellular protein that signals via the NF-κB pathway to proximally activate

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• which when subjected to the reductive opening of the aziridine ring was transformed into the pyrrolidin-2-one (4R,5S)-158. Basic hydrolysis produced (3R,4S)-155. Other amino acids: Calyculins were isolated from marine sponges and they are of interest because of possible applications as protein

Host–guest interactions in nor-seco-cucurbit[10]uril: novel guest-dependent molecular recognition and stereoisomerism

• Xiaodong Zhang,
• Wei Wu,
• Zhu Tao and
• Xin-Long Ni

Beilstein J. Org. Chem. 2019, 15, 1705–1711, doi:10.3762/bjoc.15.166

• ]. Keywords: fluorescent; host–guest interaction; macrocycles; molecular recognition; nor-seco-cucurbit[10]uril; pyrene; Introduction Host–guest interactions that trigger molecular recognition are a current topic of interest. For example, understanding the protein–ligand molecular recognition is of paramount

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• with the aim of excluding pH-dependent charge effects and to simulate a protein environment. The introduction of a methyl amide function at the C-terminus of glycopeptides was carried out on solid phase. The N-methylation of the peptide terminus on solid support was an efficient four-step procedure

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• resulting protein conformation was allowed to relax to ensure that the found conformation was an energy minimum. This protein structure was then used for docking of ligands using Glide [22][23][24]. Glide XP docking positioned both AbC and the analog atrop-O-benzyl-desmethyl-abyssomicin C with low energy

• compound 2 docks in a similar way, filling the same subpocket, maintaining the key interactions and positioning the Cys-263 near the reacting double bond (Figure 2A). The additional ring system of atrop-O-benzyl-desmethyl-abyssomicin C does not seem to make any significant interaction with the protein

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• bioinformatics as well as spectroscopy. First, we analyzed whether the isolated natural product possesses a D- or L-configured thiazoline ring. Previous studies had revealed that the D-thiazoline ring in pyochelin is due to an unusual methyltransferase-like epimerization domain in the biosynthesis protein PchE

• , 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; TE, thioesterase. The asterisk indicates a methyltransferase-like epimerization domain. C) UV

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• and complexity-generating processes [2][3] have proven success in peptide ligation [4] and macrocyclization [5][6], protein glycoconjugation [7], lipidation of peptides [8] and glycosides [9], and carbohydrate modification [10]. A special class of lipidic biomolecules are the steroids, which can be

• the natural cationic peptide antibiotics [60] or as a way to constrain peptide sequences in protein epitope conformations [61]. In this regard, the groups of Rivera and Wessjohann have pioneered the utilization of MCRs for the conjugation of oligosaccharides [62] and peptides [63][64] to steroids

Self-assembly behaviors of perylene- and naphthalene-crown macrocycle conjugates in aqueous medium

• Xin Shen,
• Bo Li,
• Tiezheng Pan,
• Jianfeng Wu,
• Yangxin Wang,
• Jie Shang,
• Yan Ge,
• Lin Jin and
• Zhenhui Qi

Beilstein J. Org. Chem. 2019, 15, 1203–1209, doi:10.3762/bjoc.15.117

• chemical synthesis [7]. In fact, supramolecular technology has shown great importance in various kinds of functional materials, including natural protein complexes [8][9][10], hydrogels [11][12][13], carbon-based materials [14][15][16][17], self-healing materials [18][19][20][21][22][23], and composite

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• -based phylogenetic analyses. Results and Discussion Whole genome-based phylogenetic analyses of Streptomyces species Genome sequences from 93 Streptomyces species for which a complete genome was available (represented by a single scaffold and a complete list of annotated protein sequences), were

• filter and download the nucleotide and protein sequences of all complete genomes including an annotation file in GFF format. The 93 selected sequences and their accession numbers are listed in Table S2 (Supporting Information File 1). Construction of orthologous gene families Sequence data of the

• pipeline. Phylogenetic analyses Phylogenetic analyses on three different terpene synthases (geosmin synthases, 2-MIB synthases and epi-isozizaene synthases) were performed. Protein and nucleotide sequences were extracted from the Streptomyces genomes based on their distribution. Phylogenetic trees were

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• forms. For example, aryl cyclopropyl sulfones have been used in the preparation of glucokinase (GK) activators for the treatment of type 2 diabetes [1][2][3][4][5] while aryl cyclopropyl sulfoximines have been utilized for the synthesis of modulators of glucokinase regulatory protein (GKRP) [6][7][8

Extending mechanochemical porphyrin synthesis to bulkier aromatics: tetramesitylporphyrin

• Qiwen Su and
• Tamara D. Hamilton

Beilstein J. Org. Chem. 2019, 15, 1149–1153, doi:10.3762/bjoc.15.111

• groups become oriented above and below the plane of the porphyrin ring, forming a protective shroud around the reactive center, much like some protein systems (Figure 1B) [12][20][21][22]. The corresponding substituted benzaldehydes, however, have not easily yielded results upon reaction with pyrrole

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• –protein interactions [19][20], CRISPR genome editing [21][22][23], DNA data storage [24][25], synthetic biology [26], bioconjugation [27] and others [28][29][30]. These applications frequently require modified ODNs that contain a wide variety of functional groups including those that cannot survive known

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• cavity [71]. Conclusion The binding pockets within enzymes, lectins, and related protein receptors are amphiphilic; that is, they contain a mixture of polar and non-polar functional groups. The macrocyclic tetralactams highlighted in this review are biomimetic in that they are synthetic host molecules

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• galectin-1 (pdb id 1GZW) and galectin-3 (pdb id 1KJL), respectively, and with the 4-fluorophenyltriazol ring protruding away from the protein. The simulations with 1b and galectin-1 converged toward a complex geometry in which the 4-fluorophenyltriazole extended along a shallow groove formed by Trp68-Gly69