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

• Streptomyces olivaceoviridis) [77][78]. This secreted protein was crystallized in 2010 by Patra et al., however, a three-dimensional structure has yet to be resolved [79]. Recently Nogueira et al. detected high titers of IgG antibodies against sMTL-13 in sera from TB patients, a response found to be diminished

• shown as blue arrows. B) sMTL-13 (aa28-155), encoded by Rv1419, showed with 100% confidence sequence similarity to a ricin B-like lectin of Streptomyces olivaceoviridis, the sequence identity was 22%. C) Known domain structure of HBHA (Rv0475): Transmembrane domain (TM), coiled coil domain, and heparin

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

• of rapamycin) [34]. This natural product, isolated from Streptomyces hygroscopicus, was one of the first protein–protein interaction stabilizers reported: it first binds to its receptor (i.e., FKBP12) with high affinity, after which the FKBP12-rapamycin complex will associate with TOR resulting in

• displayed no activity [67]. Historically, natural products have been one of the most fruitful sources to obtain antibacterial lead compounds [5][68][69]. Griselimycin, a cyclic depsidecapeptide isolated from Streptomyces sp., was discovered fifty years ago, nonetheless, due to its poor pharmacokinetic

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• , as they possess biologically validated structures, which could become suitable leads in drug discovery [2]. Recently, our research group reported the first total synthesis of leopolic acid A (Figure 1), a fungal metabolite from a terrestrial-derived Streptomyces sp. isolated from the rhizosphere of

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• the plant Vellozia magdalenae [6]. Recently, prehydropyrene (6) was discovered as biosynthetic intermediate towards the diterpene hydropyrene from the Gram-positive bacterium Streptomyces clavuligerus [7]. The six- and ten-membered rings of eunicellane diterpenoids can be either cis or trans fused

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• pathway for the synthesis of the naturally occurring antibiotic platensimycin (154) which is isolated from Streptomyces platensis. In this report, 6-methoxy-1,4-naphthoquinone-4-ethylene ketal (153) was synthesized by intermolecular oxidative cyclization of 7-methoxy-α-naphthol (152) with ethylene glycol

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• exemplified by leukotriene E4 (8) isolated from the mast cells and extensively studied for allergy and asthma [11]. Another example is grisemycin (9) from Streptomyces griseus M268, which contains an unusual ether-bridged system and a methylsulfinyl substituent [12]. Cyclothiocurvularin (10), isolated from

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• masked as a hemiketal in bafilomycins, e.g., in bafilomycin A1 [11][12][13][14]. Bafilomycins are a family of macrolide antibiotics isolated from actinobacteria such as Micromonospora and Streptomyces species [11]. They are specific inhibitors of vacuolar ATPase (V-ATPase) [15]. The most studied compound

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• sizes of B. cepacia ATCC25416, Paraburkholderia terrae DSM 17804, and Caballeronia glathei DSM50014 are 8.61, 10.1, and 8.64 Mbp, respectively, which are comparable to 9.05 Mbp for Streptomyces coelicolor A3(2) and 9.14 Mbp for Myxococcus xanthus DK 1622, both known as representatives of prolific

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• anthracycline discovered that was extracted from Streptomyces peucetius, a species of actinobacteria, at the beginning of the 1960s. Shortly after, the isolation of doxorubicin (Dox) from a mutated Streptomyces strain was accomplished. Anthracyclines are consisted of a tetracyclin aglycon part and a daunosamine

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• diastereomer was assigned by X-ray analysis. Finally, one of the products was selectively reduced to provide a functionalized analogue of streptopyrrolidine, a marine natural product isolated from Streptomyces sp. As shown in Table 1, our studies started with the synthesis of dimer 2a using azlactone 1a in the

• (Scheme 3). Compound 2c was dissolved in a mixture of acetic acid and NaBH4, cooled to 0 °C to afford the highly functionalized (+/−)-streptopyrrolidine analogue 6 in 70% yield as a unique diastereomer. Streptopyrrolidine was isolated from the marine bacterium Streptomyces sp. and has exhibited a

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• Hui Hong Markiyan Samborskyy Katsiaryna Usachova Katharina Schnatz Peter F. Leadlay Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK 10.3762/bjoc.13.238 Abstract Clethramycin from Streptomyces malaysiensis DSM4137, and mediomycins (produced together with clethramycin

• from Streptomyces mediocidicus), are near-identical giant linear polyenes apparently constructed from, respectively, a 4-guanidinobutanoate or 4-aminobutanoate starter unit and 27 polyketide extender units, and bearing a specific O-sulfonate modification at the C-29 hydroxy group. We show here that

• polyene clethramycin (1a, Scheme 1), originally isolated as an antifungal and as an inhibitor of pollen tube outgrowth from a plant-associated Streptomyces hygroscopicus strain [5]. Clethramycin (together with desulfoclethramycin (1b)) is also a product of the prolific strain Streptomyces malaysiensis

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

• acceptor. UGT74B1, involved in glucosinolate biosynthesis (see supra), was one of these 17 enzymes. Other studies have identified S-GT activities when assaying the catalytic promiscuity of O-GT with a wide range of aglycone acceptors (Figure 3). OleD from Streptomyces antibioticus has been the first

• [39] or Mangifera indica [40] (Figure 4). Fungi C-glycosyltransferases were also identified in Streptomyces, including UrdGT [41][42] and SsfS6 [43] that catalyse the transfer of the unusual D-olivosyl carbohydrate moiety on the aglycon acceptor. Bacterial C-GTs are the last group identified in

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• (−)-bornyl diphosphate synthases from the plants Salvia officinalis and Tanacetum vulgare forming a more polar product by the unusual termination via reattack of diphosphate [1], the trichodiene synthase from the fungus Trichothecium roseum [2], and pentalenene synthase from Streptomyces exfoliatus [3

• reports: [7][8][9][10][11][12][13][14]). One possible method to investigate the products of terpene synthases is the expression of terpene synthase genes in a heterologous host, as was recently performed for a large number of bacterial enzymes in an engineered Streptomyces avermitilis strain from which

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• , anhydroisoheximide (4), cycloheximide (5), and isocycloheximide (6), were obtained from the cultures of Streptomyces sp. SC0581. Their structures were elucidated by extensive spectroscopic analysis in combination with theoretical conformational analysis and ECD computations. The photoinduced interconversion between

• important to the activities of cycloheximide congeners. Keywords: antifungal activity; cycloheximide derivatives; E/Z photoisomerization; Streptomyces sp; theoretical conformational analysis; Introduction The glutarimide-containing antibiotics represent a fascinating class of natural products that exhibit

• without the toxic side-effects could provide a viable lead of therapeutic drugs or agricultural pesticides. During the course of our searching for bioactive microbial metabolites [8][9], a culture extract of Streptomyces sp. SC0581 was found to show antifungal activity against the phytopathogen

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block

• Yuta Isoda,
• Norihiko Sasaki,
• Kei Kitamura,
• Shuji Takahashi,
• Sujit Manmode,
• Naoko Takeda-Okuda,
• Jun-ichi Tamura,
• Toshiki Nokami and
• Toshiyuki Itoh

Beilstein J. Org. Chem. 2017, 13, 919–924, doi:10.3762/bjoc.13.93

• developed. These compounds have exhibited strong inhibition activity; however, they have a broad spectrum toward enzymes of various species including animals (Figure 1). N,N,N-Trimethyl-D-glucosaminyl (TMG)-chitotriomycin (1) was isolated from Streptomyces anulatus by Kanzaki [5][6][7] and the first total

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• , Kisarazu, Chiba 292-0818, Japan 10.3762/bjoc.13.47 Abstract Butyrolactol A is an antifungal polyketide of Streptomyces bearing an uncommon tert-butyl starter unit and a polyol system in which eight hydroxy/acyloxy carbons are contiguously connected. Except for its congener butyrolactol B, there exist no

• valine and its C-methylation with methionine and the polyol carbons are derived from a glycolysis intermediate, possibly hydroxymalonyl-ACP. Keywords: biosynthesis; butyrolactol; contiguous polyol; hydroxymalonyl-ACP; polyketide; Streptomyces; tert-butyl; Introduction Actinomycetes produce structurally

• diverse secondary metabolites with pharmaceutically useful bioactivities. Importantly, members of the genus Streptomyces have been the main source of drug discovery programs due to their high capacity in secondary metabolism including polyketides, peptides, terpenoids, alkaloids, and amino acid

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• derivatives were originally isolated from microorganisms [37][38], e.g., the fosmidomycin [39] is as an antimalarial drug that was isolated from broths of bacteria of the genus Streptomyces [40]. The γ-aminophosphonates were prepared through numerous synthetic methods [41][42][43][44][45]. For instance, they

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• the teicoplanin-related A47934 (sta) GPA biosynthetic machinery from Streptomyces toyocaensis [33] (Figure 1a) have revealed that the X-domain is in fact far from an innocent bystander during peptide oxidation and that switching this domain to other homologues can affect the selectivity of the Oxy

A non-canonical peptide synthetase adenylates 3-methyl-2-oxovaleric acid for auriculamide biosynthesis

• Daniel Braga,
• Dirk Hoffmeister and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 2766–2770, doi:10.3762/bjoc.12.274

• (Figure 2) [10]. Of particular interest, the occurrence of two sequential adenylation (A) domains is a very rare feature and only preceded by PyrG from Streptomyces pyridomyceticus [11]. Since the lack of a genetic system for H. aurantiacus makes the use of reverse genetics prohibitive, we sought to

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• as components of the mannopeptimycin antibiotics, isolated from Streptomyces hygroscopicus LL-AC98 in 2002 [7] and to date, have not been isolated as the free amino acids or observed in any other natural products. Natural products containing enduracididine and hydroxyenduracididine Enduracidin A and

• B Enduracidin A (7) and B (8) were first isolated from Streptomyces fungicidicus B 5477 from a soil sample collected in Nishinomiya, Japan (Figure 2) [1]. Detailed reports of the isolation procedures, in vivo and in vitro antimicrobial activity, physical properties and structure elucidation have

• been published [1][8][9][10][11][12][13][14][15]. Enduracidin A (7) and B (8) have also been isolated from Streptomyces sp. NJWGY366516 [16], Streptomyces atrovirens MGR140 [17] and along with five analogues with various halogenation patterns, from a genetically altered strain of Streptomyces

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• -cineol synthase from Streptomyces clavuligerus was investigated using stereospecifically deuterated substrates. In contrast to the well investigated plant enzyme from Salvia officinalis, the reaction proceeds via (S)-linalyl diphosphate and the (S)-terpinyl cation, while the final cyclisation reaction is

• reactions (reviewed in [25]). While the stereochemical course of the GPP cyclisation to 1 has been investigated for the 1,8-cineol synthase from Salvia officinalis [26][27], it is unknown for the bacterial enzyme that was recently reported from Streptomyces clavuligerus [28]. Here we describe isotopic

• cyclases are monodomain enzymes (α) [9][10][36]. Accordingly, also the 1,8-cineol synthases from Salvia officinalis and from Streptomyces clavuligerus are not related and have evolved independently. While the plant enzyme was shown to convert GPP via (R)-LPP ((R)-5) and the (R)-terpinyl cation ((R)-6) into

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• (marginolactones) azalomycin and kanchanamycin, isolated respectively from Streptomyces malaysiensis DSM4137 and Streptomyces olivaceus Tü4018, the first extension module catalyses both the first and second cycles of polyketide chain extension. To confirm the integrity of the azl gene cluster, it was cloned intact

• on a bacterial artificial chromosome and transplanted into the heterologous host strain Streptomyces lividans, which does not possess the genes for marginolactone production. When furnished with 4-guanidinobutyramide, a specific precursor of the azalomycin starter unit, the recombinant S. lividans

• gene cluster for biosynthesis of the polyketide β-lactone ebelactone in Streptomyces aburaviensis has shown that, contrary to a recently-published proposal, the ebelactone polyketide synthase faithfully follows the colinear modular paradigm. Keywords: colinearity; ebelactone; enzyme catalysis

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• coupling [53][54]. The oxidative cyclization diastereoselectively led to the THF diol 13 in 88% yield from which neodysiherbaine A (14) was obtained in a further three steps. Ionomycin Ionomycin (19), an ionophore antibiotic isolated from Streptomyces conglobatus in 1978 [55][56][57], has a high affinity

• . Venustatriol (96) could then be obtained by C–C-coupling with the corresponding THP fragment in an enantioselective fashion. Glaciapyrrol A Glaciapyrrol A (100), B and C form a family of pyrrolo sesquiterpenoids which have been isolated in 2005 from a marine Streptomyces sp. (NPS008187) by Macherla et al. [161