O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• glycans in pathogens or parasites, numerous other lectins recognize such O-alkylated ligands, e.g., the pilus adhesin from Pseudomonas aeruginosa PAK [31] or PapG from Escherichia coli [32]. In contrast, methylation of lectin ligands can also prevent binding, as observed with O-methylated fucose and

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• Michaela Prothiwa David Szamosvari Sandra Glasmacher Thomas Bottcher Department of Chemistry, Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany 10.3762/bjoc.12.277 Abstract The human pathogen Pseudomonas aeruginosa uses the pqs quorum sensing system to

• coordinate the production of its broad spectrum of virulence factors to facilitate colonization and infection of its host. Hereby, the enzyme PqsD is a virulence related quorum sensing signal synthase that catalyzes the central step in the biosynthesis of the Pseudomonas quinolone signals HHQ and PQS. We

• for the development of customized PqsD inhibitors as well as a chemical toolbox to investigate the activity and active site specificity of the enzyme. Keywords: activity-based probes; PqsD; protein labelling; Pseudomonas aeruginosa; quinolones; Introduction The emergence of multi-drug resistant

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• clinically important antibiotic against Gram-positive bacteria, which consists of a mixture of pseudomonic acids from Pseudomonas fluorescens NCIMB 10586 with pseudomonic acid A (61) being the main compound (Scheme 9) [37][38][39][40][41][42][43][44]. It belongs to the group of trans-AT-PKS products and the

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• , UK Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore 138671 10.3762/bjoc.12.137 Abstract Pyocyanin is a small molecule produced by Pseudomonas aeruginosa that plays a crucial role in the pathogenesis of infections by this notorious opportunistic pathogen. The inhibition

• pathogenicity of P. aeruginosa and there is a wide range of other potential applications where the inhibition of quorum sensing is desirable. Keywords: antibacterial; antivirulence; Pseudomonas aeruginosa; pyocyanin; quorum sensing; Findings The Gram-negative bacterium Pseudomonas aeruginosa is a clinically

• -oxododecanoyl)-L-homoserine lactone (OdDHL) and it’s cognate receptor LasR (Figure 1) [20][21][22]. Interlinking these two AHL signalling systems is a third signaling system utilising a quinolone signalling molecule (termed Pseudomonas quinolone signal, PQS) [20] to form an intricate hierarchical signaling

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• activity against Gram-positive bacteria, Pseudomonas and M. tuberculosis [48]. The related liposidomycins display good activity against M. phlei, while they are not active against a range of other bacteria [45]. Mode of action To develop an effective antibiotic one needs to choose a target that is

• anti-Pseudomonas agents [115]. These Gram-negative bacteria possess an outer membrane which acts as an additional permeability barrier, making them generally less sensitive to antibacterial agents. In this context, the aforementioned muraymycin analogues (91a, 92a–h) were tested for MraY inhibitory

• activity again, with MraY enzyme from S. aureus (Table 3). However, antibacterial activities against several Pseudomonas strains were moderate to low with MICs between 8 μg/mL and >64 μg/mL. Analogue 92g was the most active congener in this series with MIC values between 8 μg/mL and 32 μg/mL. Compounds 92e

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• -stoichiometric substituents in the OPS has been reported for phytopathogens Pseudomonas syringae [29] and Xanthomonas campestris [30] as well as for beneficial rhizobacteria, including free-living Azospirillum spp. [31][32][33][34][35] and root-nodulating Rhizobium spp. [24]. Moreover, the degree of acetylation

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• C (57, Figure 14), which have been isolated from different Pseudomonas strains [62][63]. Compounds 55 and 56 had been initially tested positive for antimycobacterial and antiparasitic activities and both inhibited fatty acid biosynthesis [62]. The new derivative 57, possessing a longer eastern acyl

• moiety, was identified in Pseudomonas sp. GM30, and it was subsequently proven by heterologous expression experiments with ketosynthase which is responsible for the biosynthesis of these derivatives [63]. 1.3 Monobenzo-α-pyrones Synthetic derivatives of the natural product 4-hydroxycoumarin are widely

• ]. Recently, the biosynthetic origin of the pseudopyronines A (55) and B (56) in Pseudomonas putida BW11M1 was clarified – and again two chains are fused to yield the final products [86]. Thus, it can be assumed that this mechanism is exemplified quite often in natural products. Therefore, in the next

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• potent toxin that can ward of natural predators such as wolf spiders [48]. The initial isolation of pederin (3) included the collection and chemical analysis of 250,000 beetles. Later, the true producer was found to be an endosymbiotic Pseudomonas sp. within the female beetle which was identified by

Highly stable and reusable immobilized formate dehydrogenases: Promising biocatalysts for in situ regeneration of NADH

• Barış Binay,
• Dilek Alagöz,
• Deniz Yildirim,
• Ayhan Çelik and
• S. Seyhan Tükel

Beilstein J. Org. Chem. 2016, 12, 271–277, doi:10.3762/bjoc.12.29

• ] reported the optimal pH values were 7.0 for both free FDH and immobilized FDH onto polydopamine-coated iron oxide nanoparticles (PD-IONPs). The optimum pH values of the both free Pseudomonas sp. 101 FDH and its immobilized form onto glyoxylagarose were reported as 7.0 [16]. The temperature–activity

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• study the sulfur source in tropodithietic acid (TDA, 74, Scheme 13) biosynthesis [78]. TDA is a marine antibiotic which was originally isolated from Pseudomonas species [79] showing no observable resistance in important pathogens up to now [80]. The biosynthesis of the tropone core proceeds via the

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• utilise H2 as an electron donor for the reduction of CO2 [118]. Furthermore, there is a growing list of examples of non-acetogenic metallo-FDHs, naturally catalysing formate oxidation, found to also be capable of catalysing CO2 reduction in vitro. FDH from Pseudomonas oxalaticus was the first isolated

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• their ability to catalyse selective C–H bond oxidations under mild conditions [2]. The soluble bacterial camphor monooxygenase P450cam (CYP101A1, EC 1.14.15.1) from Pseudomonas putida is one of the most studied P450s and has been engineered to accept a variety of non-natural substrates including aryl

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• violaceum (67 µg/mL), and Pseudomonas stutzeri (no inhibition), and also against the fungus Mucor hiemalis (8.3 µg/mL). The antimicrobial activity of indiacen B (2) against M. diernhoferi, which was described by Müller et al. [5] in course of the isolation from the myxobacterium Sandaracinus amylolyticus

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• of Trichophyton mentagrophytes (MIC 6.2 µg/mL) and Epidermophyton floccosum (MIC 1.6 µg/mL) [87]. Though no activity was observed against the gram negative bacteria Escherichia coli and Pseudomonas aeruginosa, meridine (56) significantly inhibited the growth of the gram positive bacteria Bacillus

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• mechanism of pyrone formation has been investigated by amino acid exchange and bioinformatic analysis. Additionally, the evolutionary origin of PpyS has been studied by phylogenetic analyses also revealing homologous enzymes in Pseudomonas sp. GM30 responsible for the biosynthesis of pseudopyronines

• with OleA. As expected, the remaining 51 sequences show a higher similarity to PpyS and the newly formed PpyS branch shows a separation into two distinct groups with PpyS and PyrS (pseudopyronine synthase) being present in one of them. The homologue PyrS from Pseudomonas sp. GM30 is described below

• pyrone biosynthesis we analyzed the KS from Pseudomonas sp. GM30, as we knew that α-pyrone antibiotics pseudopyronine A (9) and B (10) have been isolated in two Pseudomonas strains but neither their biosynthesis nor the involved KS had been reported yet [28]. Both compounds have been described to show an

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• inhibitory activity against the Gram-negative bacteria, such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa. In contrast, almost all the tested N-alkyl saponins were found to inhibit the growth of the Gram-positive bacteria (Table 2). Among the

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• avenae subsp. Citrulli, Erwinia amylovora, Pseudomonas syringae pv. Lachrymans, Clavibacter michiganense subsp. Sepedonicus, and Pectobacterium carotovorum subsp. carotovorum) and fungi (Rhizoctonia solani Kühn, Rhizotonia cerealis van der Hoeven, Phytophthora capsici Leonian, Fusarium moniliforme Sheld

• colorectal cancer, were evaluated with the MTT assay [16][17]. Antimicrobial activities against a variety of plant pathogenic bacteria (Xanthomonas oryzae pv. oryzae Swings, Xanthomonas oryzae pv. oryzicola Swings, Acidovorax avenae subsp. Citrulli, Erwinia amylovora, Pseudomonas syringae pv. Lachrymans

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• -hydroxybenzoate, benzyl alcohol, 2-phenoxyethanol) [45]. The authors established a clear relationship between the binding constants and the antimicrobial activity of the preservatives on various strains: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and C. albicans. Indeed, highly water-soluble

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• , inhibition of bacterial QS was recently demonstrated by a set of electrophilic probes (which included halogenated analogues of AHLs) that could covalently bind in the LasR binding pocket of Pseudomonas aeruginosa [15]. Therefore, designing analogues with small reactive moieties, such as halogenated carbon

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• glycoclusters based on a triazine core bearing D-galactose and L-fucose epitopes are able to inhibit biofilm formation by Pseudomonas aeruginosa. These multivalent ligands are simple to synthesize, are highly soluble, and can be either homofunctional or heterofunctional. The galactose-decorated cluster shows

• good affinity for Pseudomonas aeruginosa lectin lecA. They are convenient biological probes for investigating the roles of lecA and lecB in biofilm formation. Keywords: antibiotic; biofilm; glycocluster; lectin; multivalency effect; multivalent glycosystems; Introduction Pseudomonas aeruginosa (PA

• . The 6-deoxymannose isostere 15 was not tested, in view of the low affinity of the β-fucose epitopes. These clusters thus represent a readily accessible, highly soluble, and convenient tool for the investigation of the role of lecA and lecB in the formation of biofilms by Pseudomonas aeruginosa

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• previously reported from Pseudomonas [2][3]. The biosynthesis of 1 starts from phenylalanine and requires the paaABCDE and paaG genes of the upper phenylacetic acid (PAA) catabolon [4][5], the six genes tdaABCDEF that are located on a plasmid [6][7], and the adjacent paaZ2 gene [8], a mutated copy of paaZ

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• efficient multivalent ligands for a series of pathological lectins. For instance, cholera toxin is bound rather efficiently by calix[4]arene [16] and calix[5]arene [17] derivatives, while examples of Pseudomonas aeruginosa LecB binding were reported with galactosylcalixarenes blocked in different

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• lectins such as ConA [43] and the LecA lectin from Pseudomonas aeruginosa [17]. With these closely related families of mannosylated dendrimers in hand, together with their known relative size in solution, we are now well positioned to evaluate their binding behavior against their cognate proteins and this

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

• Aritra Chaudhury,
• Sajal K. Maity and
• Rina Ghosh

Beilstein J. Org. Chem. 2014, 10, 1488–1494, doi:10.3762/bjoc.10.153

• the A-band polysaccharide of Pseudomonas aeruginosa. One of the key steps involved 6-O-deoxygenation of either partially or fully acylated 4,6-O-benzylidene-1-thiomannopyranoside by radical-mediated redox rearrangement in high yields and regioselectivity. The D-rhamno-thioglycosides so obtained

• -rhamno-trisaccharide; deoxygenation on thioglycoside; multivalent glycosystems; one-pot sequential glycosylation; Pseudomonas aeruginosa; Introduction With the firm establishment of the critical roles played by oligosaccharides in diverse biological processes [1][2][3][4], the field of oligosaccharide

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• purification, catalytically active P450 systems were reconstituted by addition of putidaredoxin (Pdx) and putidaredoxin reductase (PdR) from Pseudomonas putida as well as the pyridine cofactor NADH. Reactions were performed in 500 µL reaction volume. In order to avoid the stoichiometric addition of NADH