The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• 2-methylisoborneol from (S)-2-Me-LPP may be explained by isomerization to 2-Me-GPP and then to (R)-2-Me-LPP. Keywords: biosynthesis; enantioselective synthesis; enzyme mechanisms; gas chromatography; terpenoids; Introduction After its first discovery from Streptomyces [1][2], it has been

• recognized that many soil bacteria including various genera from the actinobacteria [3][4][5][6][7] and myxobacteria [8] produce the volatile musty odour compound 2-methylisoborneol (1). The compound is also found in marine Streptomyces strains [9] and aquatic cyanobacteria that can cause drinking water

• ]. Recent research on its chemical ecology demonstrated that arthropodes are attracted by compound 1 which helps in the dispersion of Streptomyces spores [20]. The absolute configuration of (–)-1 has been established through a synthesis from (+)-camphor [21]. The biosynthesis of compound 1 was initially

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• naturally occurring HDAC inhibitors are known to date [12]. Acyclic molecules like, e.g., trichostatin A (TSA, Figure 1) were among the first isolated HDAC inhibitors. Isolated in 1976 from Streptomyces hygroscopicus by Tsuji et al. [13], TSA played an important role in rationalizing the mode of action of

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

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• S3). Using dimethylallyl diphosphate (DMAPP) and (E)- and (Z)-(4-13C,4-2H)isopentenyl diphosphate (IPP) [18] in conjunction with FPP synthase (FPPS) from Streptomyces coelicolor [19] and PTS (Supporting Information File 1, Figure S11), stereogenic centres of known configuration are introduced at the

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

• the genus Streptomyces [11], non-Streptomyces actinomycetes, commonly referred to as rare actinomycetes [12], are attracting considerable attention as less tapped taxa for drug discovery. Those within the family Micromonosporaceae, represented by the second most prolific genus Micromonospora following

• Streptomyces, are especially noted, accounting for more than 800 metabolites of actinomycetes origin [11], which include the antiinfective aminoglycoside gentamicin [13], antidiabetic glycoside acarbose [14], glycopeptide antibiotic teicoplanin [15], enediyne antitumor component of drug-antibody conjugate

• products from Couchioplanes sp. RD010705. The α,γ-dimethyl-α,γ-dienoyl C8 motif in 1, 2, 4, and 5 is only precedented by 64p-B (2,4-dimethyl-2,4-octadienamide) produced by manumycin-producing Streptomyces, though the physicochemical properties of which is yet to be disclosed [28]. The γ,ε-dimethyl-α,γ

Host–guest interaction and properties of cucurbit[8]uril with chloramphenicol

• Lin Zhang,
• Jun Zheng,
• Guangyan Luo,
• Xiaoyue Li,
• Yunqian Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 2832–2839, doi:10.3762/bjoc.17.194

• Streptomyces venezuelae [1], which has a certain inhibitory effect on many Gram-positive and -negative cocci bacteria, as well as anaerobic bacteria [2], and is used for the treatment of typhoid, meningitis, chlamydia, eye infections, purulent wounds and other diseases [3]. Chloramphenicol is slightly soluble

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• biologically. Prekinamycin (76) and isoprekinamycin (77) are diazo compounds isolated from Streptomyces murayamensis that differ in their ring system, with the former containing a fused 6-6-5-6 skeleton and the latter containing a 6-5-6-6 skeleton. Due to their similarity and common source, it had been

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• Anwei Hou Jeroen S. Dickschat Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany 10.3762/bjoc.17.161 Abstract The sesterterpene synthase SmTS1 from Streptomyces mobaraensis contains several unusual residues in positions that

• from Streptomyces mobaraensis (SmTS1) represents the first identified type I sesterterpene synthase (StTPS) from bacteria [16]. This enzyme converts GFPP into multiple products seven of which could be isolated and structurally characterised as sestermobaraenes A–F (1–6) and sestermobaraol (7) (Figure 2

• ). SmTS1 has a low amino acid sequence identity to other characterised TPSs, with the diterpene synthase (DTS) for cattleyene from Streptomyces cattleya as one of the closest relatives, which shows only 29% sequence identity [17]. We have recently shown that the sum of the calculated van der Waals volumina

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• natural occurrence of methylated prequeuosine bases stems from a recent study that demonstrated that m6preQ0 is produced by Streptomyces [17]. Moreover, the natural products huimycin [18] and dapiramicin contain m6preQ0 as core with their 2-NH2 group linked to a 2'-acetamido-2'-deoxy-ß-ᴅ-glucopyranosyl

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• than 70% of them are produced by the genus Streptomyces [1]. However, intensive and concentrated screening activities on soil actinomycetes resulted in the repeated isolation of known compounds [2], which consequently prompted the exploration of untouched niches, such as extreme environments [3]. The

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

• Streptomyces lasaliensis cultures [195]. The synthesis succeeded in five steps, each one of them in good yields, including the cobalt-catalyzed C–H bond addition (Scheme 37D). One year later, the same group described a unique cobalt-Cp* catalyzed C(sp2)–H amidation technique [196] applied to thiostrepton (125

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

• address: MSD UK Discovery Centre, Francis Crick Institute, 1 Midland Road, London, NW1 1AT, United Kingdom 10.3762/bjoc.17.31 Abstract A one-flask, two-step procedure from 3-amino-2-methyl-5,6,7,7a-tetrahydro-1H-pyrrolizin-1-one affords the Streptomyces secondary metabolites legonmycins A and B – three

• a chemical and biosynthetic perspective. Their emergence dates back to 1977 with a patent filing from The Upjohn Company describing an unidentified ‘antibiotic 354’ isolated as a fermentation product of Streptomyces puniceus subsp. doliceus; spectroscopic characterization, including 1H NMR data, was

• , 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

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

• , complex mixture, such as a culture medium, using 19F NMR. The earliest example of the technique being applied in this was in the discovery of fluoroacetate and 4-fluorothreonine in cultures of the bacterium Streptomyces cattleya [111]. 19F NMR became a cornerstone for investigating the biosynthesis of

• 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

• Bidyut Kumar Senapati Department of Chemistry, Prabhat Kumar College, Contai, 721404, India, Tel.: +91 8145207480 10.3762/bjoc.17.7 Abstract The inthomycin family of antibiotics, isolated from Streptomyces strains, are interesting molecules for synthesis due to their characteristic common oxazole

• -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

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• enzymatic conversion of the correspondingly 13C-labelled isoprenyl diphosphate precursors with the sestermobaraene synthase from Streptomyces mobaraensis. The main compounds sestermobaraenes A, B, and C were analysed by gas chromatography–mass spectrometry (GC–MS), allowing for a deep mechanistic

• investigation of the electron impact mass spectrometry (EIMS) fragmentation reactions of these sesterterpene hydrocarbons. Keywords: isotopes; mass spectrometry; reaction mechanisms; sesterterpenes; Streptomyces mobaraensis; Introduction The sestermobaraenes A–F (1–6) and sestermobaraol (7) are a series of

• bacterial sesterterpenes that were recently discovered by us from the actinomycete Streptomyces mobaraensis through a genome mining approach (Figure 1) [1]. All seven compounds are produced by a canonical terpene synthase, representing the first reported sesterterpene synthase of the classical type I from

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• [1]. More than 10,000 secondary metabolites have been isolated from actinomycetes, accounting for almost 45% of all known microbial secondary metabolites. Particularly, 70% of them were isolated from the genus Streptomyces, the dominant genus commonly found in terrestrial environments [2]. The number

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• , National Institute of Technology and Evaluation (NBRC), Kisarazu, Chiba 292-0818, Japan 10.3762/bjoc.16.97 Abstract Aside from the well-studied conventional actinomycetes such as Streptomyces, the less investigated genera of actinomycetes also represent a promising source of natural products. Genome

• widely used as an indicator of the taxonomic position of prokaryotes. It was believed that a high similarity of the 16S rRNA gene sequence implied the closeness or even the identity in other sets of genes including secondary metabolite biosynthetic genes. However, our recent analysis of Streptomyces

• actinomycetes” refers to non-Streptomyces actinomycetes [12] and the representative genera, such as Micromonospora, Actinomadura, Nocardia, Actinoplanes, and Saccharothrix, which are no longer rare in terms of difficulties in isolation, already provided thousands of new metabolites [13][14]. Meanwhile, the

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• , Dept. of Chemistry, Technical University of Munich (TUM), Lichtenbergstr. 4, 85748 Garching, Germany 10.3762/bjoc.16.7 Abstract Terpene cyclases are responsible for the initial cyclization cascade in the multistep synthesis of a large number of terpenes. CotB2 is a diterpene cyclase from Streptomyces

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• expression is the most widely used method to study complex terpenoid biosyntheses. Since many bacterial terpenoid BGCs are actinomycete-derived, terpene BGCs are often expressed in model Streptomyces hosts, such as Streptomyces albus, Streptomyces avermitilis, Streptomyces coelicolor, and Streptomyces

• lividans, under the control of exogenous promoters [92][93][94]. To minimize the cellular resource competition and facilitate cleaner analysis, many of these hosts have been engineered to remove native secondary-metabolite BGCs and for optimized terpene precursor supply [1][95][96][97]. Like Streptomyces

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

• , Technical University of Munich (TUM), Lichtenbergstr. 4, 85748 Garching, Germany Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel 10.3762/bjoc.15.228 Abstract CotB2 catalyzes the first committed step in cyclooctatin biosynthesis of the soil bacterium Streptomyces melanosporofaciens. To

• exclusively belong to class I TPSs. A few exceptions exist, for example the terpentedienyl-diphosphate synthase from Kitasatospora griseola [19], which belongs to class II, and PtmT1 from Streptomyces platensis in the platensimycin gene cluster [20], which is neither characteristic for class I nor class II

• cyclooctatin biosynthetic gene cluster in particular the TPS CotB2 from the soil bacterium Streptomyces melanosporofaciens MI614-43F2 (Figure 1) [31]. Cyclooctatin 5, with its distinct 5–8–5 ring motif, belongs to the fusicoccane diterpenoids that encompass a wide range of bioactivities, such as bacteriostatic

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

• /bjoc.15.115 Abstract Terpene synthases are widely distributed among microorganisms and have been mainly studied in members of the genus Streptomyces. However, little is known about the distribution and evolution of the genes for terpene synthases. Here, we performed whole-genome based phylogenetic

• analysis of Streptomyces species, and compared the distribution of terpene synthase genes among them. Overall, our study revealed that ten major types of terpene synthases are present within the genus Streptomyces, namely those for geosmin, 2-methylisoborneol, epi-isozizaene, 7-epi-α-eudesmol, epi-cubenol

• , caryolan-1-ol, cyclooctat-9-en-7-ol, isoafricanol, pentalenene and α-amorphene. The Streptomyces species divide in three phylogenetic groups based on their whole genomes for which the distribution of the ten terpene synthases was analysed. Geosmin synthases were the most widely distributed and were found

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

• from Phalaris coerulescens (Figure 3). Likewise, maremycins [13] and spirotryprostatin B [14] have been isolated from marine Streptomyces and from the fermentation broth of Aspergillus fumigatus. Among benzo-fused γ-lactam chemical entities, natural and synthetic isoindolinones are a prominent class of

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• configuration of 1. For 1, C-5 was targeted by (1R)- and (1S)-(1-13C,1-2H)GPP [28], which were enzymatically elongated with isopentenyl diphosphate (IPP) by farnesyl diphosphate synthase (FPPS) from Streptomyces coelicolor [29] with a known stereochemical course [30] (Figure S4, Supporting Information File 1

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• terpinyl cation has been investigated using deuterium labelling, demonstrating different stereochemical courses in the plant Salvia officinalis [8][9] and in the bacterium Streptomyces clavuligerus [10]. Also the highly unusual methylated sesquiterpene sodorifen (4) possesses a mirror plane [11] making any