Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• CsrA, which is a promising target for new anti-infective compounds. However, drug development is hampered by poor cellular uptake [86][87]. In the biosynthesis of cypemycin in Streptomyces sp. OH-4156, CypM adds two methyl groups to the N-terminal alanine residue. Cypemycin has a very narrow activity

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• system and the C2–C3 alkene, are instilled by these terpene synthases. Four types of eunicellane synthases are known (Figure 1B). The first eunicellane synthase identified, Bnd4 from the biosynthesis of benditerpenoic acid in Streptomyces sp. (CL12-4) [5], forms a cis-eunicellane named benditerpetriene

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• -acyltransferase polyketide synthase biosynthetic gene cluster sdl (80 kb) from Streptomyces sp. B59 was cloned and transferred into a heterologous host, Streptomyces albus J1074, resulting in the production of a class of polycyclic macrolide shuangdaolides A (1), B, and D and dumulmycin (2) [29]. Furthermore

• Streptomyces sp. MSC090213JE08, and constructed recombinant strains with forced expression of each of the seven SARP genes. When these were cultured in four different media and examined for metabolic profiles, a total of nine unknown metabolites were found in the four SARP-expressing strains under specific

• groups, using a ribosome engineering approach in Streptomyces sp. CB02009 (Figure 2d) [48]. Seyedsayamdost et al. developed the high-throughput elicitor screening (HiTES) approach, a forward chemical genetics method that identifies small-molecule inducers of silent natural products (Figure 2e) [49]. Han

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• understanding of the acidic lipopeptide structure–activity relationship (Scheme 4b). Surugamide B The cyclic octapeptides surugamides were isolated from several Streptomyces sp. and shown to be cathepsin B inhibitors [56][57][58]. According to a biosynthetic viewpoint, the corresponding modules consist of four

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

• [4]. To further understand the role of the ANS pathway in secondary metabolism, we recently identified the BGC for avenalumic acid (ava cluster, see the lower right corner of Figure 1B for its structure) by genome mining targeting the ANS pathway in Streptomyces sp. RI-77, and revealed its entire

• µM and adding AvaA7 (final concentration: 0.2 µM) and NADPH (final concentration: 800 µM). Comparison of ava and cma clusters and the biosynthetic pathway of p-coumaric acid. A) Schematic representation of ava and cma clusters from Streptomyces sp. RI-77 and Kutzneria albida, respectively. They

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

• biosynthesis of 28 is so far limited to bacteria. Finally, a terpene synthase homolog from Streptomyces sp. Tü 2975 was investigated in this study (Table 1, entry 15). The enzyme contains all conserved sequences with a slightly modified aspartate-rich motif (88DDFIV) and the NSE triad 227NDRYSFCKE, and is with

• an amino acid sequence identity of 85% closely related to the recently reported sesterviolene synthase from Streptomyces violarus (SvSS) [52]. Accordingly, also the enzyme from Streptomyces sp. Tü 2975 catalysed the conversion of GFPP into sesterviolene (29, Figure 8C and 8D), but GPP, FPP and GGPP

• were not taken as substrate. The newly identified enzyme was designated Streptomyces sp. Tü 2975 Sesterviolene Synthase (StSS). Conclusion Despite the accumulated knowledge on bacterial terpene synthases, the scattered distribution of sesqui-, di- and sesterterpene synthases in the phylogenetic tree of

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• .18.166 Abstract Longicatenamides A–D are cyclic hexapeptides isolated from the combined culture of Streptomyces sp. KUSC_F05 and Tsukamurella pulmonis TP-B0596. Because these peptides are not detected in the monoculture broth of the actinomycete, they are key tools for understanding chemical

• the combined-culture strategy and new labeling reagents has led to the detection and structural determination of several unprecedented secondary metabolites [5][6][7]. Longicatenamides A–D (1–4, Figure 1) are cyclic hexapeptides isolated from the combined-culture of Streptomyces sp. KUSC_F05 and T

• developed [4]. Among the isolated longicatenamides, compound 1 exhibits weak but preferential antimicrobial activity against Bacillus subtilis. Because peptides 1–4 are not detected in the monoculture broth of Streptomyces sp. KUSC_F05, they are key tools for understanding chemical communication in the

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• the discovery of N–N bond-containing natural products from our in-house actinobacterial culture collection, we found two closely related potential biosynthetic gene clusters of aliphatic azoxy natural products in Streptomyces sp. RM72 and Streptomyces sp. A1C6 (Figure 2 and Tables S1 and S2 in

• Streptomyces sp. RM72 were first partitioned by water and ethyl acetate, and then the organic layer was further fractionated by silica gel column chromatography. Fractionation by reversed-phase HPLC yielded ten compounds (1–10) that generate N2H4 upon acid hydrolysis. The combination of 1H and 13C NMR with a

• discovered from Streptomyces sp. strain P8-A2 (Figure 3a) [21]. Of note, the trans-azodyrecins 4–6 are reportedly generated by the spontaneous isomerization of the cis-congeners, after long-term exposure to CHCl3 [21]. While trans-azodyrecins could also be generated nonenzymatically from their cis-congeners

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• Chinese Academy of Sciences, Beijing 100049, China 10.3762/bjoc.18.101 Abstract Two novel diarylcyclopentenones daturamycin A and B (1 and 2), and one new p-terphenyl daturamycin C (3), along with three known congeners (4–6), were isolated from a rhizosphere soil-derived Streptomyces sp. KIB-H1544. The

• C (3), and three known p-terphenyl derivatives (4–6) (Figure 1) were isolated from the fermentation extract of Streptomyces sp. KIB-H1544. Structurally, daturamycins A and B are uncommon diarylcyclopentenone compounds that consist of a tricyclic 6/5/6 system instead of a C-18 tricyclic skeleton in

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• , as well as two possible producers (Streptomyces sp. San01 and Kitasatospora sp. CB02891) after a survey of the existing genome sequence databases, however, we discovered a strain, Kitasatosporia griseola DSM 43859, without a genome sequence disclosed, from the strain library of CGMCC. Using the

• ent-CPP into the target tetracyclic skeleton, ent-kaurene (Figure 2). In this study, the ent-CPP synthase (eCDPS) gene was cloned from Streptomyces sp. NRRL S-1813, which was an alternative ent-kaurenol-derived antibiotic platensimycin producer [33][34][35], while the ent-kaurene synthase (BjKS) gene

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• saturated congener of compounds 2 and 3. Tenacibactins K−M (1–3) are new members of desferrioxamine-type hydroxamate siderophores [28]. The preceding congeners are tenacibactins A–D produced by Tenacibaculum sp. [18] and tenacibactins E–J produced by Streptomyces sp. [29]. Siderophores of this class are

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• necessary for their biosynthesis. Prenylated indoles are widely distributed among bacteria, fungi and plants, and all seven positions are subject of prenylation except for the bridgehead carbons [34]. Compound 6 is the acetylated derivative of 6-(3,3-dimethylallyl)-ʟ-tryptophan from Streptomyces sp. SN-593

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• , was also reported in 1980 [10]. Following a 23-year hiatus, two papers submitted within two weeks of each other reported, respectively: (1) the isolation from Streptomyces sp. UMA-044 and characterization of NP25302, that differs from bohemamine in lacking the 6,7-epoxide functionality [11] and (2

• ) the jenamidines A–C, from another Streptomyces sp. strain [12], although these molecules were not recognized as pyrrolizidines until Snider’s subsequent synthetic work revised the structural assignment [13][14] and, separately, established the absolute configuration of natural (+)-NP25302 [15

• papers addressed their biosynthesis. Thus, the investigation of the metabolites of Streptomyces sp. MA37 (from a soil sample obtained in Legon, Ghana) revealed the production of legonmycins A (3) and B (4) (Figure 2) and found that just four genes (lgnA–D) were necessary for their biosynthesis [22

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• shift changes due to minor structural differences, the observation of new fluorinated compounds in crude culture supernatants is possible. 19F NMR analysis of cultures of the bacterium Streptomyces sp. MA37, which was isolated from a Ghanian soil sample, revealed several new resonances in addition to

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• -interrupted oxazolyltriene unit is conjugated to a chiral β-hydroxycarbonyl center of an amide functionality. Inthomycin A ((+)-1), the first member of the inthomycin family, was isolated by Omura’s group from the strain of Streptomyces sp. OM-5714 in 1990 [1]. Then, the following year, Henkel and Zeek had

• reported the reisolation of inthomycin A ((+)-1) and the first isolation of inthomycin B ((+)-2) from the strain of Streptomyces sp. Gö 2, and proved inthomycin A ((+)-1) to be identical with phthoxazolin A ((+)-1) [2]. Later, the reisolation of inthomycin B ((+)-2) and inthomycin C ((–)-3) was reported by

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

• marinum; diterpene synthase (BAP82229), Streptomyces sp. ND90; tsukubadiene synthase (EIF90392), Streptomyces tsukubaensis NRRL 18488; terpene synthase (ZP_00085244), Pseudomonas fluorescens PfO-1; spiroalbatene synthase (WP_030426588.1), Allokutzneria albata; spatadien synthase (WP_095757924.1

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

• species is Streptomyces sp. SAT1 (see Table S9 (Supporting Information File 1) for a list of the isolation sources and habitats of the 93 strains). This strain is an endophyte of the flowering plant Adenophora trachelioides from the Campanulaceae family and it does contain a copy of geoA, the gene

• encoding for geosmin synthase. Some species such as Streptomyces sp. SirexAA-E harbour a silent geosmin synthase encoding gene in their genomes and do not produce this degraded sesquiterpene under laboratory culture conditions [9]. It will therefore be interesting to investigate whether the geosmin

• synthase in Streptomyces sp. SAT1 is expressed, and to further determine the role of terpenoids in the endophytic life style. The first geosmin synthase was characterised from Streptomyces coelicolor [18]. Geosmin synthases are composed of two domains that both exhibit the typical highly conserved motifs

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

• 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

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

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

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

• were referenced to the solvent signal (δH(D) 2.50). ESITOFMS were recorded on a Bruker microTOF focus. Microorganism Streptomyces sp. strain TP-A0882 was isolated from a deep seawater collected in the Toyama Bay, Japan. The strain was identified as a member of the genus Streptomyces on the basis of

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

• 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