Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• antipseudomonal activity. The biosynthetic pathway for argyrin production in Cystobacter sp. SBCb004 (Arg1, radical SAM-dependent methyltransferase; Arg2/Arg3, nonribosomal peptide synthetases; Arg4, O‑methyltransferase; Arg5, tryptophan 2,3-dioxygenase). The initial tripeptide of the biosynthesis of the argyrins

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

• potential with molecular structure is severely restricted. The canonical terpene biosynthetic pathway uses a single enzyme to form a cyclized hydrocarbon backbone followed by modifications with a suite of tailoring enzymes that can generate dozens of different products from a single backbone. This

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

• analyses above, a biosynthetic pathway to the nanangenines was proposed (Figure 3). Unlike the ast cluster, where there are multiple HAD-like enzymes encoded (one terpene synthase and two phosphatases), the putative nanangenine cluster only encodes one such enzyme, FE257_006542. However, given that

• biosynthetic gene cluster in A. nanangensis MST-FP2251 and homologs identified in other drimane sesquiterpenoid-producing species of Aspergillus section Usti. Gene models are drawn to scale; shaded boxes that link gene models represent amino acid identity (0% transparent; 100% black). Putative biosynthetic

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• (+)-valencene from germacrene A [11]. This biosynthetic pathway could also be confirmed by feeding experiments. The formation of the three aforementioned sesquiterpene hydrocarbons takes place without deuterium loss, so that with the use of d3-MVL as precursor (Scheme 5) nine deuterium atoms and with the use of

• described by Steele et al. for the formation of guaia-6,9-diene and δ-selinene via germacrene C could also be confirmed by feeding experiments (Scheme 7) [9]. Biosynthesis of (E)-β-caryophyllene and α-humulene The biosynthetic pathway postulated by Boland and Garms for the formation of (E)-β-caryophyllene

• from farnesyl pyrophosphate (FPP) is consistent with our feeding experiments (Scheme 8) [29]. The incorporation of deuterium atoms into (E)-β-caryophyllene during biosynthesis is shown by the following mass spectra (Figure 11). The assumed biosynthetic pathway for the formation of (E)-β-caryophyllene

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• [38]. HQNO acts through inhibition of complex III in the respiratory chain of bacteria and mitochondria of eukaryotes and, hence, it can be considered a general cytotoxic agent. DHQ, a shunt product of the PQS biosynthetic pathway, is important for P. aeruginosa virulence in a Caenorhabditis elegans

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• biosynthetic pathway from linoleic acid via its hydroperoxide has been suggested [24][25][26], and if the same biosynthetic steps would proceed from linolenic acid, this would result in the assigned structure of 2 (Scheme 1B). The other compounds identified in the headspace extracts of A. fischeri were all

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• -dimethylphenol (11), B) 2-hydroxy-4-methylbenzaldehyde (12), C) 3,4-dimethoxytoluene (15), D) 2-methoxy-4-methylbenzaldehyde (17), E) 2-methoxy-5-methylphenol (14), F) 5-hydroxy-2-methylchroman-4-one (18), and G) 5-hydroxy-2-methyl-4H-chromen-4-one (19). Proposed common biosynthetic pathway to volatile aromatic

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• structure could be assigned to each of the eight peaks observed in this analysis, again confirming the structure of (4R,5R,6S)-11a for the natural product from D. clavata (Figure 4). The 13C NMR data of all four stereoisomers 11a–d are summarised in Table 2. A proposed biosynthetic pathway to (4R,5R,6S)-11a

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• resemblance to cadinane-type sesquiterpenes from plants, but is structurally entirely unprecedented in bacteria. Based on its molecular architecture, a possible biosynthetic pathway is postulated. Keywords: genome mining; herpetopanone; Herpetosiphon; isotope labeling; terpene; Introduction Terpenoids

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

• aggression. Their biosynthetic pathway requires the action of a S-GT (UGT74B1) that catalyses the reaction between a thiohydroximate acceptor and UDP-α-D-glucose as sugar donor to yield the corresponding desulfoglucosinolate (Figure 2) [20][21]. UGT74B1 from A. thaliana is a versatile enzyme in terms of

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• C14’. The first and currently only mycolactone originating from a genetically engineered biosynthetic pathway was isolated by Leadlay and co-workers in 2007 [63]. Thus, the cloning of a CYP450 hydroxylase gene from a related strain into the M. marinum DL045 strain produced a mycolactone F variant with

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

• ; pink, PKS for polyketide backbone of 1; yellow, genes for biosynthesis of hydroxymalonyl-ACP; gray, transporter. Biosynthetic pathway of hydroxymalonyl-ACP. Adapted from [24]. Incorporation of L-valine-d8 into 1. (a) 1H NMR spectrum of natural 1 and 2H NMR spectrum of L-valine-d8-labeled 1. (b) ESIMS

• produced by a Streptomyces strain collected from deep sea water of the Toyama Bay, Japan. In order to get insight into the construction of the above-mentioned unusual structures, we performed an in silico analysis of the biosynthetic genes of 1 through draft genome sequencing and proposed its biosynthetic

• pathway [22]. In this study, biosynthetic precursors of 1 were investigated for further genetic and enzymatic studies. Results and Discussion It was obvious from its structure that 1 was synthesized through the malonate pathway. First, [1,2-13C2]acetate was fed to the culture to ensure the alignment of

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

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

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• (13-13C)-2, c) unlabelled 3 and (13-13C)-3, d) unlabelled 4 and (13-13C)-4, e) unlabelled 5 and (13-13C)-5, f) unlabelled 6 and (13-13C)-6. Biosynthetic pathway from FPP to 7-epi-α-eudesmol (4). NMR data of α-amorphene (1), and T-muurolol (2) in (2H6)benzene. NMR data of 4-epi-cubebol (3) and 7-epi-α

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• that is produced in Streptomyces species [134][135]. The respective biosynthetic pathway has been fully reconstituted in an in vitro one-pot reaction [136]. The flavoprotein EncM transforms the C12 methylene group of the octaketidic PKS type II product 139 in a two-step oxidation sequence using the

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• -methylisoborneol biosynthetic pathway by comparing the mass spectra of the methylated compounds to their non-methylated analogs [11]. Higher terpenes such as sesqui- and diterpenes, as being produced by terpene cyclases from oligoprenyl diphosphates, are usually (poly)cyclic compounds with different ring sizes

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• amide carbonyl by ATP (Figure 3B, pathway b), which is analogous to a reaction catalysed by PurM family enzymes (aminoimidazole ribonucleotide synthetases) in the biosynthesis of aminoimidazole ribonucleotide as part of the purine biosynthetic pathway [39] (Figure 3, inset). This activated amide would

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• higher ratios than labelled sodium mevalonate. Therefore, the authors suggested that β-oxidation of linoleic acid is a probable main step in the biosynthetic pathway of 29 in Trichoderma species [34]. The incorporation of labelled sodium mevalonate is hypothesized to be due to degradation to acetate with

• biosynthesis via norlichexanthone was ruled out by incorporation studies in Alternaria tenuis using [1-13C, 18O2]-labeled acetate. This resulted in high incorporation of acetate-derived oxygen into all the oxygen-bearing carbons [76]. A proposed biosynthetic pathway of 17 [77] (by aromatization of a polyketide

• anticoagulant drugs warfarin and phenprocoumon. Structures of selected monobenzo-α-pyrones. Hypothetical pathway of 29 generation from linoleic acid [34]. Proposed biosynthetic pathway of alternariol (modified from [77]). Malonyl-CoA building blocks are applied to build up the enzyme-bound polyketide chain

Mycothiol synthesis by an anomerization reaction through endocyclic cleavage

• Shino Manabe and
• Yukishige Ito

Beilstein J. Org. Chem. 2016, 12, 328–333, doi:10.3762/bjoc.12.35

• Gram-negative bacteria. MSH undergoes metal-catalyzed autoxidation more rapidly than glutathione [16]. The biosynthetic pathway of MSH has been well investigated; MSH is synthesized from 1-inositol phosphate and uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) in five steps [15]. It is used by

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• nine-membered carbocycle which is the characteristic structural feature of these natural products. Additionally, the putative biosynthetic pathway of xenicanes is illustrated. Keywords: asymmetric synthesis; natural products; total synthesis; Xenia diterpenoids; xenicanes; Introduction Terpenoids are

• xeniaethers. An alternative biosynthetic pathway proposed by Schmitz and van der Helm involves the direct formation of the nine-membered carbocyclic ring via oxidative cyclization of geranyllinalool (34) [2], which is formed from GGPP (28) by enzymatic hydrolysis of the pyrophosphate unit and allylic

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• carbon skeleton with an unprecedented 6/5/6 tricyclic ring system bearing an α,β-unsaturated spirolactone moiety in ring B, and represents a new subclass of norditerpenoid, the skeleton of which is named aspergilane. The hypothetical biosynthetic pathway for 1 was also proposed. The cytotoxic

• literature [18][19][20]. Structure of aspergiloid I (1) and its novel skeleton. Selected 1H,1H-COSY and HMBC correlations and key NOEs observed for 1. X-ray single-crystal structure of 1. Proposed biosynthetic pathway of 1. 1H and 13C NMR spectroscopic data for aspergiloid I (1). Supporting Information

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• metabolically engineered cell-surface sialic acids [24]. The application of 3 was prompted by the previous observation that carbamate-modified ManNAc derivatives are also accepted in the biosynthetic pathway [19][29]. Derivative 3 in combination with a sulfo-Cy3-tetrazine conjugate enabled dual sugar labeling

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• biosynthetic pathway of the hypermodified tRNA nucleoside queuosine [3]. Recently, preQ1 base has attracted considerable attention because this nucleobase specifically binds to bacterial mRNA domains and regulates genes that are required for queuosine biosynthesis, by a so-called riboswitch mechanism [4][5][6

• Jasmin Levic Ronald Micura Institute of Organic Chemistry, University of Innsbruck and Center for Molecular Biosciences Innsbruck, Innrain 80–82, 6020 Innsbruck, Austria 10.3762/bjoc.10.199 Abstract Pre-queuosine or queuine (preQ1) is a guanine derivative that is involved in the biosynthetic

• pathway of the hypermodified tRNA nucleoside queuosine (Que). The core structure of preQ1 is represented by 7-(aminomethyl)-7-deazaguanine (preQ1 base). Here, we report the synthesis of three preQ1 base derivatives with complementary 15N-labeling patterns, utilizing [15N]-KCN, [15N]-phthalimide, and [15N3

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• tropone (3) and tropone hydrate 4 can also be detected in P. inhibens headspace extracts and are shunt products of the TDA biosynthetic pathway [9]. Clardy and coworkers have recently reported on a series of structurally related compounds with algicidal activity, represented by roseobacticide A (5), but

• , and may have other physiological or ecological functions. This result is particularly surprising, because the coenzyme A ester of 13 is an intermediate along the biosynthetic pathway to TDA, so the question arises what may have been the evolutionary advantages of extending the biosynthetic pathway

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• subsequently deprotected in a one-pot fashion. Pharmacological assessment of these novel PreQ0 derivatives is currently underway in a variety of kinase-inhibitory studies and will be reported in due course. Biosynthetic pathway leading to nucleosides queuosine and archaeosine. Chemical structure of