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

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• Discussion Although the genes responsible for heronapyrrole biosynthesis have not been identified yet, it is nevertheless possible to speculate on key aspects of this biosynthetic pathway, particularly those oxidative transformations that generate structural diversity [6][7][8][9] in the farnesyl side chain

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• aqueous n-BuOH extract yielded the new compounds siphonodictyals E1–E4 (1–4) and cyclosiphonodictyol A (5). In this article, we describe the isolation, structural elucidation, and bioactivity of compounds 1–5 from the Aka growth form incrustans, as well as discuss the biosynthetic pathway of related

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• for the key role of late-stage hydroxylation at C-26 of the monensin molecule. Like other polyether ionophores, monensin is assembled by the polyketide biosynthetic pathway on a modular polyketide synthase (PKS) multienzyme [14]. A model has been proposed [14] for monensin biosynthesis in which an

• and demethylmonensin A, although it highlights the importance of the C-26 O-hydroxylation for the integrity of the ionophore structure, is not directly relevant to the (evolution of) the biosynthetic pathway. As discussed above, the final steps leading to formation of the polyether rings take place

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• of decandrinin (1) by comparing the calculated CD spectra with the experimental one. Proposed biosynthetic pathway for decandrinin (1). 1H (400 MHz) and 13C (100 MHz) NMR spectroscopic data for 1 in CDCl3 (δ ppm). Supporting Information Supporting Information File 176: HRMS (ESI) and NMR spectra of

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• the synthesis of all the three compounds 5–7 by mimicking the biosynthetic pathway. Baylis–Hillman adducts are densely functionalized synthons, which mainly consist of three different functional groups such as the ester, olefin and hydroxy group [8]. Recent developments made it possible to introduce

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

• Tao Wang,
• Patrick Rabe,
• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311

• dichlorodimethoxybenzene (10b or 10k) can arise by a second chlorination from the monochlorodimethoxybenzene (4b or 4f, respectively), suggesting that in both organisms the sets of chlorinated compounds arise via one and the same biosynthetic pathway. Known structurally related compounds from fungi are drosophilin A (19

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• biosynthetic pathway to myxocoumarins A (7) and B (9). NMR data of compound 7 at 500 (1H) and 150 (13C) MHz. Supporting Information Supporting Information File 514: NMR and MS spectra of myxocoumarin A (7) and B (9). In-depth discussion and analysis of chemical shifts for the verification of the structure of

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• 10.3762/bjoc.9.290 Abstract Antimycins (>40 members) were discovered nearly 65 years ago but the discovery of the gene cluster encoding antimycin biosynthesis in 2011 has facilitated rapid progress in understanding the unusual biosynthetic pathway. Antimycin A is widely used as a piscicide in the catfish

• biosynthetic pathway. Keywords: antimycins; gene regulation; genome mining; natural products; Streptomyces; Review It is estimated that around 60% of all known antibiotics are derived from secondary metabolites made by filamentous actinomycete bacteria, most notably Streptomyces species [1]. Streptomyces

• . Biosynthesis of the antimycin dilactone core Antimycins are produced by a hybrid non-ribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) assembly line for which the complete biosynthetic pathway has been proposed [25][34] (Figure 3). The biosynthesis of antimycins involves the activities of fourteen