Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• bacteria, fungi, mammalian cells and plants. Bioinformatics analysis, including comparative analysis with other acyl drimenol-producing Aspergilli, led to the identification of a putative nanangenine biosynthetic gene cluster that corresponds to the proposed biosynthetic pathway for nanangenines. Keywords

• cell lines, two bacteria, one fungus and one plant (Table 4). Compound 1 was inactive up to 100 μg mL−1 in all of the assays performed, suggesting acylation at 6-OH is important for biological activity. Compounds 4, 5 and 7 showed moderate antibacterial activity against B. subtilis, with weaker

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• play a key role in determining and regulating the biology of these organisms [1] and act as the elicitor of the innate immune response [2]. As these polysaccharides can protect the bacteria concerned by killing the serum complements of the host system and can stop phagocytosis, they are extremely

• bacteria present in the guts of human and other warm-blooded animals. It is usually harmless and beneficial to the host’s body, however, there are other variants of E. coli having virulence factors and causing diseases like diarrhea, urinary tract infection, septicaemia etc. E. coli O132 is reported to be

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• reported for solonamides. Keywords: antivirulence drug; bacteria; macrocyclization; pathoblocker; quorum quenching; Introduction The cyclodepsipeptides called solonamides A and B are natural molecules extracted from the marine bacterium Photobacterium halotolerans [1][2] (Figure 1). They are able to

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

• an α-helical bundle fold [18] and are structurally related to the isoprenyl diphosphate synthases such as the farnesyl (C15) or geranylgeranyl (C20) diphosphate synthase, which generate the substrates of sesqui- and diterpene synthases, respectively. In bacteria, diterpene synthases almost

• description of the bacterial TPS CotB2, we will therefore refer to the NSE motif only. Using host microorganisms, such as bacteria or baker’s yeast for the heterologous synthesis of terpenes increases the sustainability of bioactive terpene production by saving resources, as the production host can be fed

• enzymes that is widely distributed among plants, fungi and bacteria. CotB2 has evolved to convert the acyclic, achiral substrate GGDP to the 5–8–5 ring motif of cyclooctat-9-en-7-ol that contains six chiral stereocenters. Hence, CotB2 has been fine tuned to perform a highly specific regio- and

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• . Compound 1 showed weak growth inhibition against Saccharomyces cerevisiae. Keywords: biosynthesis; fatty acid; marine bacteria; methylation; Microbulbifer; Introduction Marine microbial symbionts are currently recognized as a reservoir of new bioactive compounds [1]. The most well-studied host animal is

• the sponge from which a vast array of natural products has been isolated and symbiotic bacteria are suggested to be responsible for the biosynthesis of such natural products [2]. Although it is well established that corals are associated with diverse microbes, coral-associated bacteria and their

• secondary metabolites have received lesser attention [3]. To date, a couple of new compounds were discovered from soft coral-associated bacteria such as pseudoalteromones from Pseudoalteromonas isolated from the cultured octocoral Lobophytum crassum [4][5] and macrolactin V from Bacillus amyloliquefaciens

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• play a prominent role as lead structures in drug discovery [1]. Apart from bacteria, fungi are an impressive group of microorganisms in this respect, due to the high structural diversity of their rich secondary metabolism. Fungi are known as producers of many therapeutically important drugs, such as

• For the isolation of fungal strains from terrestrial and marine environments a device was constructed, i.e., FIND that is similar to the one described by Epstein et al. for “unculturable” bacteria [4]. For the FIND we adjusted the isolation procedure and technical features, e.g., the dimensions of the

• volume of a sample is experimentally hard to determine. We thus counted bacterial cells, and applied the ratio of bacteria-to-fungi, which is described in the literature for most environments, to estimate suitable dilution or concentration steps in our experiments. Scheme 2 illustrates each individual

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• apoptotic cells, the investigation of the morphology of nuclei, the direct counting of cultivable bacteria, DNA intercalators, etc. [1][2][3][4]. Pyrrole, another biologically active heterocyclic compound, when fused with acridines affords promising bioactive pyrroloacridinone moieties demonstrating

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

• physicochemical properties that NPs typically show [3]. Abyssomicin C (AbC) is an NP with antibacterial activity that was isolated from the marine actinomycete strain Verrucosispora AB-18-032 in 2004 [4][5]. It shows antibacterial activity against Gram-positive bacteria, including resistant pathogens such as

• covalent inhibitor of 4-amino-4-deoxychorismate (ADC) synthase, which is the enzyme that catalyzes the conversion of chorismate and glutamine into ADC and glutamate, the first step in the biosynthesis of p-aminobenzoic acid (PABA) in bacteria [6]. Specifically, AbC binds via a Michael addition between a

• cysteine residue in the immediate proximity to the active site and the enone moiety of AbC. The PABA pathway is essential in bacteria but absent in humans, making AbC a promising compound for further development towards an antibiotic drug candidate. Because of its intriguing structure and antibacterial

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• substances inhibited the growth of the test microorganisms demonstrating weak antimicrobial effect (Table 2). The growth of gram-positive bacteria (strains of S. aureus and B. subtilis) was inhibited in a more effective way. Particularly, compound 11b inhibited the growth of B. subtilis at a concentration of

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

• analysis of this genus is discussed. Keywords: biosynthesis; evolution; geosmin; Streptomyces; terpenes; Introduction Streptomyces are soil bacteria that belong to the order of actinomycetales and are a rich source of natural products with broad biotechnological interest. Species of this genus have a

• revealed that terpenoids can be produced by all kingdoms of life including bacteria, fungi and protists [6][7][8][9][10]. The ability of an organism to produce terpenoids relies on whether the organism contains terpene synthase genes. Biosynthetically, the production of the different types of terpenes

• 3 [30]. These enzymes are the most widespread sesquiterpene synthases in bacteria, and their coding genes are present in the genomes of more than 100 of the sequenced Streptomyces species [13]. Interestingly, epi-isozizaene synthases are only present in members of one clade (indicated as the green

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• ]. Besides, several hybrid molecules containing, inter alia the oxindole moiety, have been discovered and they demonstrated diverse therapeutic activities, for example, against breast [46] and colon cancer cells [47] and drug-resistant bacteria [48]. Among the many excellent recent reviews on the preparation

New terpenoids from the fermentation broth of the edible mushroom Cyclocybe aegerita

• Frank Surup,
• Florian Hennicke,
• Nadine Sella,
• Maria Stroot,
• Steffen Bernecker,
• Sebastian Pfütze,
• Marc Stadler and
• Martin Rühl

Beilstein J. Org. Chem. 2019, 15, 1000–1007, doi:10.3762/bjoc.15.98

• /mL, for KB3.1 = 7 µg/mL), but was inactive against all test organisms in our standard test panel, comprising selected Gram-positive and Gram-negative bacteria as well as fungi [8]. Compound 4 was inactive in all assays of our test panel, and 3 could not be tested due to the insufficient amount

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• membrane of Gram-negative bacteria, are considered today as attractive candidates for vaccine delivery. However, they have some disadvantages, they are not easy to produce and are difficult to characterize [2][3]. Moreover, toxic lipopolysaccharides (LPS) present in the outer membrane of most of Gram

• -negative bacteria prevent the medical use of OMV from natural sources [4]. Licensed vaccines based on crude OMV are currently available to contribute to the prevention and to control at least twenty-five infections including pulmonary ones [5]. Developing synthetic vaccines against cancer [6][7] or Gram

• -negative bacteria [7] are challenges for the current research in the field. Artificial OMV, composed of synthetic and non-toxic, non-immunogenic phospholipids and glycolipids are good candidates for drug or vaccine delivery. One of the most common reactions used to prepare monoalkyl glycosides is the

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• Frankfurt, Max-von-Laue-Str. 15, D-60438 Frankfurt am Main, Germany 10.3762/bjoc.15.47 Abstract The repeated and improper use of antibiotics had led to an increased number of multiresistant bacteria. Therefore, new lead structures are needed. Here, the synthesis and an expanded structure–activity

• ; nematophin; Staphylococcus aureus; Introduction Microorganisms present a rich source of bioactive natural products of pharmacological importance against an emerging number of multiresistant bacteria [1]. Such examples are Xenorhabdus sp., Gram-negative entomopathogenic bacteria which live in symbiosis with

• soil-living nematodes of the genera Steinernema [2][3]. During a complex life cycle the nematode–bacteria pair infects and kills insect larvae, whereby Xenorhabdus produce a broad range of natural products with antimicrobial properties [4][5][6][7][8]. As the Steinernema–Xenorhabdus complex is not

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• -negative pathogenic organism causing pneumonia, urinary tract infections (UTI), intra-abdominal infections, meningitis, and pyrogenic liver abscesses in humans [1][2][3]. The bacteria have capsules in the outermost layers of the cells, which are composed of a variety of complex polysaccharides known as K

• based on the glycoconjugate derivatives of these polysaccharides. Isolation of polysaccharides by fermentation of bacterial strains suffer from a number of limitations, which include (a) handling of live strains of bacteria; (b) difficulties in separating biological impurities such as proteins or

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• collaborators described the synthesis and investigation of the bacteria urease inhibitory activity for ciprofloxacin derivatives, including the amide 2, which presented a remarkable IC50 value for urease inhibition and was capable of inhibiting Proteus mirabilis growth [14]. As another example, in a previous

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• . aeruginosa and Staphylococcus aureus, which model interactions relevant to patients with cystic fibrosis, HQNO is a major factor for killing of S. aureus [15]. While HQNO seems to be generally toxic to Gram-positive bacteria, we could show that some bacteria are able to transform HQNO into less toxic

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• Abstract The importance of bacterial lectins for adhesion, pathogenicity, and biofilm formation is well established for many Gram-positive and Gram-negative bacteria. However, there is very little information available about lectins of the tuberculosis-causing bacterium, Mycobacterium tuberculosis (Mtb

• biology and identify new drug targets and anti-Mtb strategies. Mtb bacteria are mainly transmitted by inhalation of aerosolized droplets released from infected patients by coughing. The infection process is initiated by contact between inhaled bacteria and host cells within the alveolar airspace. The main

• target cells of Mtb bacteria are primarily alveolar macrophages, which internalize the pathogen through phagocytosis [6]. These innate immune cells initiate a number of responses to limit bacterial replication and spread with the ultimate goal of eradicating the pathogen. However, Mtb has evolved

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

• bacteria in the biofilm mode including virulence mechanisms that cripple immune defenses, may offer novel antimicrobial therapies against a variety of otherwise persistent P. aeruginosa infections. Here, we screened our in-house collection of FDA-approved drugs and found that cisplatin was the most potent

• 16–18 h. MIC was taken as the lowest concentration where no visual growth (based on OD600) of bacteria was detected. The experiments were performed in triplicate and representative results were shown. RNA preparation Bacterial cells were collected using the method described previously [17] with some

• modifications. Generally, PAO1 cells were cultivated either with (1.5 μM) or without cisplatin. The cells were harvested at the early-stationary phase (after approximately 8 h cultivation). Total RNA was extracted with an RNeasy Protect Bacteria Mini Kit with on-column DNase digestion (Qiagen). A Turbo DNA-free

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• , University of Oldenburg, Carl-von-Ossietzky-Straße 9–11, 26111 Oldenburg, Germany Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, Campus E8.1, 66123 Saarbrücken, Germany 10.3762/bjoc.14.276 Abstract Bacteria of the

• Roseobacter group (Rhodobacteraceae) are important members of many marine ecosystems. Similar to other Gram-negative bacteria many roseobacters produce N-acylhomoserine lactones (AHLs) for communication by quorum sensing systems. AHLs regulate different traits like cell differentiation or antibiotic

• yet unknown function as signalling compounds in the ecology of these bacteria, although their singular occurrence is in strong contrast to the common occurrence of AHLs. Obviously the structural motif is not restricted to Roseovarius spp. and occurs also in other genera. Keywords: amino acid

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• reducing the burden of multidrug-resistant microorganisms. Protein–protein interactions (PPIs) are involved in a myriad of vital cellular processes and have become an attractive target to treat diseases. Therefore, targeting PPI networks in bacteria may offer a new and unconventional point of intervention

• to develop novel anti-infective drugs which can combat the ever-increasing rate of multidrug-resistant bacteria. This review describes the progress achieved towards the discovery of molecules that disrupt PPI systems in bacteria for which inhibitors have been identified and whose targets could

• medicine. Unfortunately, since their use is intrinsically linked to the appearance of resistance, threatening antibiotic-resistant bacteria levels are being observed, compromising the efficacy of nearly all available antibiotics to cure infectious diseases [2][3][4]. The rise in the percentage of

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• Gram-negative bacteria [38]. They constitute up to 24 strands, require sophisticated assembly machineries for membrane integration [39] and are usually “plugged” by hydrophilic loops and helices that either ensure the binding of small molecules, or their (energy-dependent) transport across the outer

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• hypothesized that by “disarming” the pathogen, rather than inhibiting its growth, selective pressure for resistance development will be much lower. Furthermore, reduction of bacterial virulence directly protects the host, and at the same time renders the bacteria more susceptible towards the host defense

• system and antibiotics. The Centers for Disease Control and Prevention (CDC) have listed a number of bacteria that present serious, urgent and concerning threats [8]. One of these problematic bacteria is methicillin-resistant Staphylococcus aureus (MRSA), a human pathogen that causes a wide range of

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• development [9] and further biological evaluations [10]. The disaccharide motif is also commonly found in viruses and bacteria. In bacteria, as an example, it has been found in pathogenic bacteria such as in Salmonella [11], Shigella [12], several Burkholderia [13], Escherichia coli [14], Vibrio chlorae [15

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• -position, there is a structural resemblance to the Pseudomonas quinolone signal (PQS), and its biosynthetic precursor 2-heptyl-4(1H)-quinolone (HHQ), which are vital to the cooperative behaviour of the human pathogen Pseudomonas aeruginosa via quorum sensing (QS). This is a means by which bacteria alter

• for compounds 3 and 4 was erroneously switched). It is tentatively proposed that this is as a result of disruption of electron transport, as the compounds bear resemblance to the menaquinones which are used by bacteria for this purpose [10]. Following on from this, we recently reported a divergent

• bacterial density as measured by OD600 (no significant effect on the overall growth of the bacteria was observed for any of the compounds, see Supporting Information File 1 for details). The most promising results were replicated to ensure validity (due to the large amount of chemicals required for the