Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• large number of natural products are reported representing this scaffold [9][10][11][12][13][14][15][16]. The key precursor used in the biosynthesis of β-carboline is ʟ-tryptophan which forms the basis of great abundance of β-carboline-containing natural products [17]. A broad spectrum of biological

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• ) [32], the terpene precursor of compounds 4–6. Meanwhile, direct deprotonation of cadinyl cation (J) generates the double bond Δ9,10 of 1,5-cadinadiene (N) [32], the precursor of compound 7. Compounds 4–7 belong to the phenolic sesquiterpenes family, and the biosynthesis of the phenolic group has not

• characterized the function of a P450 enzyme CYP76AH1 which was responsible for the formation of the aromatic ring of ferruginol in the biosynthesis pathway of tanshinones [34]. Hence, we proposed that the oxidation occurred on L to furnish the aromatic ring of calamenene (M) [29], followed by the hydroxylation

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

• reconstructed two-step artificial pathway efficiently produced IPP and DMAPP and thus can be used to overproduce the clerodane and ent-kaurane diterpenes in E. coli. Collecting the essential genes in the biosynthesis of terpentetriene and ent-kaurene Terpentetriene and ent-kaurene are labdane-related diterpenes

• ]. In the biosynthesis of terpentetriene, GGDP was first cyclized by a class II DTS (Cyc1) that contains a conserved DxDD motif to form terpentedienyl diphosphate (TDP) via a syn-labda-13-en-8-yl+ diphosphate intermediate (Figure 2), which, prior to deprotonation, can be followed by rearrangement to

• Information File 1) [31]. These results demonstrated that the two-step artificial pathway coupled with downstream genes for the terpentetriene and ent-kaurene biosynthesis was successful and efficient. Though a single plasmid expression system might lower the host cell burden, our results showed that the two

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

• ]. 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

• biosynthesis of 1 can also be reconstituted in vitro through coupling of dimethylallyl diphosphate (DMAPP) with 2-methyl-IPP (2-Me-IPP; IPP = isopentenyl diphosphate) to 2-Me-GPP using farnesyl diphosphate synthase (FPPS), followed by cyclization through 2MIBS to 1 [26]. A recently described methyltransferase

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• preferences. While the microbial UbiA Ptase catalyzes the C–C-bond formation between an isoprenyl chain and the meta-position of p-hydroxybenzoate (PHB) in the ubiquinone-Coenzyme Q10 biosynthesis (Figure 1), Ptases of type MenA perform the key step in the menaquinone biosynthesis by prenylating 1,4-dihydroxy

• ) contained close homologs of the bacterial MenA family (EC 2.5.1.74) (50–100% pairwise identity) catalyzing the key step in the menaquinone biosynthesis [2]. As marine bacteria such as Zobellia barbeyronii [16] Marinithermus hydrothermalis [17], Marinobacter litoralis [18], and Marinobacter flavus [19] have

• been reported to produce menaquinone 6 (MK-6), it can be speculated that G1-Ptases of this group are likely involved in its biosynthesis. The second group of Ptases (G2) included yet poorly described UbiA-like Ptases (EC 2.5.1.39) with 43–99% pairwise identity. The third cluster of Ptases (G3) (20–100

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• endoperoxygenase NvfI. Keywords: biosynthesis; endoperoxide; enzyme; natural products; X-ray crystallography; Introduction Endoperoxide-containing compounds form a large group of natural products with cyclic peroxide structures [1][2][3][4][5]. These compounds are widely distributed in nature, and many

• endoperoxide-containing natural products, numerous synthetic analyses and biosynthesis of endoperoxide compounds have been reported [18][19][20][21]. In some cases; e.g., in the biosynthesis of artemisinin and ergosterol peroxides, a reactive oxygen species (ROS) such as singlet oxygen, which is generated by

• photosensitizers or visible light, non-enzymatically reacts with the biosynthetic intermediates to produce endoperoxide structures [16][22][23]. However, over the past three decades, only a few endoperoxide-forming enzymes have been identified, including the cyclooxygenases in the biosynthesis of prostaglandins

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• . [27] or reviewed by Plutschack et al. [28]. In the current work pressures up to 130 MPa were achieved by using an ultrahigh-performance liquid chromatography (UHPLC) pump. Results and Discussion Immobilization For the biosynthesis of N-acetylneuraminic acid, two enzymes, the epimerase from Pedobacter

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• been reported before. The isolated metabolite 5 represents the previously described siderophore amamistatin B [7], while compound 6 was before only known as a decomposition product of a synthetically prepared obafluorin derivative [8]. Results and Discussion To induce siderophore biosynthesis in N

• reductive degradation of amamistatin-type siderophores. Compound 6 represents a possible shunt product of amamistatin biosynthesis. A similar molecule and its putative biosynthetic pathway were recently described by Jaspars et al. [12]. In accordance with this proposal, salicylic acid and ʟ-threonine would

• data. The newly found compounds are assumed to represent intermediates or shunt products in amamistatin biosynthesis. In comparison to amamistatin B, they exhibit a lower iron affinity, which can be ascribed to the lack of hydroxamate groups. Experimental Analytical methods LC–MS analysis was performed

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

• results from these experiments are contradictory. The present work reports on a reinvestigation of patchoulol biosynthesis by isotopic labelling experiments and computational chemistry. The results are in favour of a pathway through the neutral intermediates germacrene A and α-bulnesene that are both

• reactivated by protonation for further cyclisation steps, while previously discussed intra- and intermolecular hydrogen transfers are not supported. Furthermore, the isolation of the new natural product (2S,3S,7S,10R)-guaia-1,11-dien-10-ol from patchouli oil is reported. Keywords: biosynthesis; DFT

• alternative biosynthetic mechanism that also starts with a cyclisation of FPP to A (Scheme 2A) [10], but then a subsequent deprotonation to 8, an important neutral intermediate in the biosynthesis of many sesquiterpenes [11], is assumed. A reprotonation-induced cyclisation leads to E that is again

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

• , a similarly methyl-branched unsaturated fatty acid ester, which is produced by type I polyketide synthase in a Streptomyces strain by a heterologous expression experiment [33]. These facts suggest that 1–5 could be byproducts from the biosynthesis of larger polyketides, but further investigation is

• 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

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• has been reported for benzylisoquinoline alkaloids, including spasmolytic, narcotic, dopaminergic, ion-channel modulating, and cytotoxic properties. Occurrence, biosynthesis and pharmacology of benzylisoquinoline alkaloids has been reviewed comprehensively by Hagel and Facchini [1]. Synthetic

• approaches to the monomeric 1-benzyl-1,2,3,4-tetrahydroisoquinoline alkaloids are typically inspired by their biosynthesis and comprise Bischler–Napieralski-type cyclizations of arylacetamides (followed by reduction of the resulting 3,4-dihydroisoquinolines) or Pictet–Spengler-type cyclizations of

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

• , tandem reactions, and the total synthesis and biosynthesis of natural products. This review explores the use of α-ketol rearrangements in these contexts over the past two decades. Keywords: acyloin rearrangement; asymmetric synthesis; iminol rearrangement; ketol rearrangement; tandem reactions

• biosynthesis of delitschiapyrone A could occur non-enzymatically in nature by a similar process. The final example of a tandem reaction involving an α-ketol rearrangement in a total synthesis was employed by Chen et al. in the preparation of (±)-securinine (54) and (±)-allosecurinine (55), biological alkaloids

• part of their mechanism. Ketol-acid reductoisomerase (KAR), which is involved in the biosynthesis of branched-chain amino acids, takes as its substrate either (2S)-acetolactate (60, R = Me), which is ultimately converted into valine or leucine, or (2S)-acetohydroxybutyrate (60, R = Et), which

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

• , turning SmTS1 from a sesterterpene into a diterpene synthase. This article gives rational explanations for these findings that may generally allow for protein engineering of other terpene synthases to improve their catalytic efficiency or to change their functions. Keywords: biosynthesis; enzyme

• (GFPP, C25) for sesterterpene biosynthesis. Type I terpene synthases (TPSs) activate these acyclic molecules by the abstraction of diphosphate to produce a reactive allyl cation that can initiate a cascade reaction through typical carbocation chemistry, including cyclisation reactions by intramolecular

• the Q227D enzyme variant. Regarding the active site contouring residues, the G184L resulted in a completely disrupted sesterterpene biosynthesis, which supports the hypothesis that SmTS1 exhibits an unusually large active site cavity capable of taking up GFPP, while the enzyme variants with larger

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• (see Supporting Information File 1). The biosynthesis hypotheses of compounds 1–5 were proposed to have originated as an extension of the reported pseudomonine (6) biosynthesis [37][38][39][40] via the salimethyloxazolinyl-thioester intermediate 8 (Figure 3). We speculated that compounds 1–3 occur

• hypotheses not previously reported in natural product biosynthesis. Experimental General experimental procedures IR spectra were acquired on a Perkin Elmer Spectrum Two FT-IR spectrometer equipped with an ATR diamond cell. Optical rotations were measured on an ADP 410 digital Polarimeter (Bellingham

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

• this end, robust synthetic routes towards O6-alkylated 7-aminomethyl-7-deazaguanines are urgently needed and reported here. Results and Discussion Biological and synthetic background Role of preQ1 in queuosine biosynthesis and gene regulation Queuine (Q base) is a derivative of guanine that is involved

• thereby regulates genes that are required for queuosine biosynthesis [8][9][10][11][12][13][14][15][16]. The molecular mechanism behind is called riboswitching. For most riboswitches, ligand binding induces a structural change in the untranslated leader sequence of mRNA by formation (or disruption) of a

• queuosine (Q), the natural products dapiramicin A and huimycin, as well as intermediates of queuosine biosynthesis (preQ1 and preQ0), and the major synthetic targets of this study, m6preQ0 (1) and m6preQ1 (2) (grey box). Synthesis of compound 1 (m6preQ0) by cyclocondensation using a 4-methoxypyrimidine

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• , temperature and aeration, are known to regulate gliotoxin biosynthesis [115][119][120]. The biological activity of ETP’s like gliotoxin is mediated by the active disulfide bridge that targets vulnerable thiols or catalyses oxidative burst formation via redox cycling [78]. In previous studies, these cytotoxic

• of its biosynthesis are well established: the 19 kb gene cluster contains 6 genes and lies downstream of the conidiation pathway. The polyketide synthase PksP combines the starter units acetyl-CoA and malonyl-CoA into the heptaketide naphthopyrone YWA1 (11). The hydrolytic activity of Ayg1 shortens

• prenylation of fumigaclavine A leads to fumigaclavine C (19), the final product of fumigaclavine biosynthesis [159]. Biosynthesis of the intermediate festuclavine as well as fumigaclavines A–C is dependent on LaeA regulation [124]. Its numerous bioactive effects hold the potential for a pharmaceutical use

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• , State University of New York, Buffalo, NY 14260, USA 10.3762/bjoc.17.119 Abstract Glycosylation is a common posttranslational modification, and glycan biosynthesis is regulated by a set of glycogenes. The role of transcription factors (TFs) in regulating the glycogenes and related glycosylation

• health and disease may affect multiple carbohydrate structures. Upon applying the Fisher’s exact test along with glycogene pathway classification, we identified TFs that may specifically regulate the biosynthesis of individual glycan types. Integration with Reactome DB knowledge provided an avenue to

• various sources in literature [45][46]. The following is a summary of the pathways studied and the enzymes involved: 1) Glycolipid core: The enzymes in this group are involved in the biosynthesis of the glucosylceramide (GlcCer) and galactosylceramide (GalCer) lipid core. Here, the GlcCer core is formed

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• stronger defense response against the beet armyworm (Spodoptera exigua) [81]. In these cases, it is not known whether the increased terpene emission results from biosynthesis by the plant or the fungus. Future work should include measurements of plant and fungal TPS expression to determine the origin of

• two terpene synthases from one of the endophytic fungi to lay the groundwork for comparing the biosynthesis of plant vs fungal volatiles. More knowledge about the formation of these compounds could contribute to the greater understanding of their roles in plant–insect, plant–plant and plant–microbe

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• high concentrations during saline stress conditions [32]. It has not yet been described in the Ulva–bacteria symbiosis. Not all essential genes for ectoine biosynthesis reported by [33] were found in the U. mutabilis genome [34], providing further support for the bacterial origin of ectoine. Homologs

• aspartokinase (ask_ect). Aspartokinase (Ask), along with ʟ-aspartate-β-semialdehyde-dehydrogenase (Asd), provides the precursor ʟ-ASA for ectoine biosynthesis [33][44][45]. Homologs of the enzymes of the ectoine pathway from Halorhodospira halochloris were identified by BLAST searches of the U. mutabilis genome

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• biomedical applications due to their ability to inhibit the glycan and glycosaminoglycan biosynthesis [34][35][36][37]. The fluorine substituent has typically been introduced into these GlcNAc and GalNAc analogues using nucleophilic fluorination. The primary position (C6 hydroxy group) was fluorinated by

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• those of the central nervous system, where they function in intercellular recognition and communication. We describe an in silico method for determining the metabolic pathways leading to the most common gangliosides, based on the known enzymes of their biosynthesis. A network of 41 glycolipids is

• ganglioside biosynthesis, and altered ganglioside status in cancer, and the effects on network structure are predicted. The simulator is available at the Glycologue website, https://glycologue.org/. Keywords: gangliosides; Glycologue; glycosyltransferases; neuropathy; Svennerholm nomenclature; Introduction

• negative charge. Figure 1 shows the structure of the monosialylated ganglioside GM1a. The biosynthesis of gangliosides occurs in the endoplasmic reticulum and Golgi, where specific glycosyltransferases act, in stepwise fashion, by adding monosaccharides from sugar nucleotide donors, first to ceramide, and

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• first protein-biosynthesis-generated structures are based on variable backbone elements; proline (cyclic and chiral), glycine (acyclic and achiral) or alanine (acyclic and chiral). Subsequent acquisition of the functional side-chains for this repertoire led to the recruitment of amino acids that are

• pathways for proline biosynthesis involve the synthesis from either glutamate or ornithine [61]. Both sources of amino acids are derived from the core metabolic processes. The connection to the central metabolism makes it difficult to make interventions in the production of proline in the cells. For

• entry into the citric acid cycle. The dehydrogenation of proline is involved in numerous biochemical processes. For example, the dehydrogenation of proline linked to an acyl carrier protein makes a first step in the biosynthesis of some neurotoxins from cyanobacteria (ana gene cluster) [68]. The

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• from the roseobacter group is the production of the sulfur-containing antibiotic tropodithietic acid (TDA) in Phaeobacter piscinae DSM 103509T [28], a compound that is in equilibrium with its tautomer thiotropocin [29] that was first described from Pseudomonas sp. CB-104 [30]. Its biosynthesis depends

• experiments also led to a suggestion for the mechanism for sulfur incorporation, but further research is required for a deep understanding of TDA biosynthesis. Besides its function as an antibiotic, TDA acts as a signaling molecule, similar to N-acylhomoserine lactones, at concentrations 100 times lower than

• required for a significant antibiotic activity [34]. The biosynthesis of tropone [35] and of the algicidal sulfur-containing roseobacticides [36] are most likely connected to the TDA pathway. Interestingly, in the interaction with marine algae P. inhibens can change its lifestyle from a symbiotic