Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• ; enzymatic capping; methyltransferase; RNA; Introduction The 5′-cap is a hallmark of eukaryotic mRNA and involved in numerous interactions required for cellular functions. Chemically, the 5′-cap consists of an inverted 7-methylguanosine connected to the rest of the eukaryotic mRNA via a 5′–5′ triphosphate

• responsible guanylyltransferase uses GTP as substrate and forms a covalent enzyme-(lysyl-N)-GMP intermediate, reminiscent of DNA ligase-AMP intermediates [30][31]. Finally, the cap structure is methylated at the N7-position by an RNA(guanine-N7)methyltransferase using S-adenoysl-L-methionine (AdoMet) as a

• -terminal half and the methyltransferase in the C-terminal half of the large D1 protein, whereas the small D12 protein has no catalytic activity but activates D1 [36][37][38]. Originally, the RNA capping with the Vaccinia capping apparatus was reported to be inefficient [35][37][39][40]. To date, the enzyme

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• pharmacological activities. For example, abafungin (Figure 1) is an antifungal drug marketed worldwide for the treatment of dermatomycoses. It works by inhibiting the enzyme sterol 24-C-methyltransferase [1][2][3][4]. Febuxostat, also known by its brand name adenuric is a xanthine oxidase inhibitor that helps to

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

• hydroxymalonyl-ACP formation in the zwittermicin biosynthesis (ZmaN, ZmaD, ZmaG, and ZmaE) (Figure 6) [24] are present in the downstream of the butyrolactol PKS cluster. Genes coding for O-methyltransferase homologues responsible for O-methylation of hydroxymalonyl-ACP were not found near the cluster

• coding for C-methyltransferase are not present near the butyrolactol PKS genes. Further enzymatic studies are necessary to establish the order of the starter loading/C-methylation events. Conclusion In summary, we elucidated the biosynthetic origin of butyrolactol A (1) on the basis of the feeding

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• optional mono- or dimethylation of azalomycin at the guanidino group, and the attachment of a malonyl sidechain at either C-23 or C-25 (Figure 1). No methyltransferase or discrete malonyltransferase is encoded within the respective BGCs. Comparison of the bioinformatic prediction for either marginolactone

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

• mechanism is reminiscent of the formation of a tetrahydropyridine ring by the berberine bridge enzyme in plant alkaloid biosynthesis. It starts with S-adenosyl-L-methionine (SAM)-dependent methylation of the secondary hydroxy group in 81 by the O-methyltransferase Leu14 (Scheme 14a) [71][72][73][74

• lactone that is decarboxylated towards the xanthone [103]. Studies with recombinant AflM and a lack of isolatable intermediates however made it clear that the order of steps in demethylsterigmatocystin (107) formation needs to be carefully re-evaluated [100]. Methylation by an O-methyltransferase and

• -one 129 by action of the O-methyltransferase JerF [50]. 1.6.2 Michael addition–lactonisation: A novel mechanism for the integration of pyran-2-ones into polyketide backbones has recently been discovered. Rhizoxin. In 2013, Hertweck and co-workers provided detailed insight into the unprecedented enzyme

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• ). Generating B. subtilis mutant strains, overexpressing the bpsA gene, yielded in triketide pyrenes. Once the adjacent gene bpsB, the latter coding for a methyltransferase, was co-overexpressed, the methylated variants, i.e., triketide pyrone methyl ethers, were synthesized. The pyrone-forming activity of BpsA

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• of catechol-O-methyltransferase [11], matrix metalloproteinases, carboxy-peptidase A, collagenase and thermolysin [12]. The biological activity of derivatives of 1,2-tropolone was the impetus for the rapid development of various methods for the synthesis and study of biological activity of these

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• the addition of thiol reagents like dithiothreitol. This property makes the cross-linking reaction fully reversible and allows for a switching of the linked base pair from locked to unlocked during biochemical experiments. Using the DNA methyltransferase from Thermus aquaticus (M.TaqI) as example, we

• ; DNA methyltransferase; nucleic acids; oligodeoxynucleotide; thionucleoside; Introduction Covalent interstrand DNA cross-links have long sparked clinical and biochemical interest. The cytotoxicity of bisfunctional alkylating agents like nitrogen mustards or chloroethyl nitrosourea (CENU) derivatives

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

• undergoes a cascade of ring opening/closing catalysed by the combined action of the unusual epoxide hydrolases MonBI and MonBII, to give the putative protein-bound intermediate dehydroxydemethylmonensin. The next steps, catalysed respectively by the cytochrome P450 hydroxylase MonD and the methyltransferase

• specifically-blocked mutant of wild-type S. cinnamonensis [24] or from a wild-type fermentation conducted in the presence of the potent methyltransferase inhibitor metapyrone [25]. To gain further insight into the metal-binding properties of demethylmonensin A and dehydroxymonensin A, they were each

Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

• Dinesh Simkhada,
• Huitu Zhang,
• Shogo Mori,
• Howard Williams and
• Coran M. H. Watanabe

Beilstein J. Org. Chem. 2013, 9, 1768–1773, doi:10.3762/bjoc.9.205

• implicated a pyruvate aldolase and methyltransferase containing gene cluster as well as potential polyketide gene clusters containing methyltransferase genes, which will be evaluated in due course through genetic knockout experiments of the ΔaziA2 mutant strain. Disruption of the aziA2 gene gave

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• group of endophenazine A forming an amide bond to the α-amino group of L-Gln. Gene inactivation experiments in the gene cluster proved that ppzM codes for a phenazine N-methyltransferase. The gene ppzV apparently represents a new type of TetR-family regulator, specifically controlling the prenylation in

• methyltransferase that catalyzes the N-methylation reaction during the biosynthesis of pyocyanine in Pseudomonas. Also, Streptomyces anulatus produces an N-methylated phenazine, i.e., endophenazine B [22]. The heterologous expression strain S. coelicolor M512 containing the endophenazine cluster from S. anulatus

• the first phenazine N-methyltransferase gene identified in Streptomyces. We expressed the protein PpzM in E. coli and purified it using Ni2+ affinity chromatography. However, incubation of PpzM with S-adenosylmethionine and either PCA or dihydro-PCA did not result in the formation of any methylated

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• the chain elongation with malonyl-CoA, followed by methylation with SAM by catalysis of a C-methyltransferase. Indeed the incorporation of isotopic labelling into the α- and γ-methyl branched FAMEs was observed with high incorporation rates (>90%, Figure S5 of Supporting Information File 1

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• extension with malonyl-CoA. The mechanism by which this truncation occurs is currently unknown (Figure 4A). Further unique features of microcystin biosynthesis include the standalone aspartate racemase McyF [22], the O-methyltransferase McyJ [23] and the 2-hydroxy-acid dehydrogenase McyI [24]. In addition

• domain; PCP: Peptidyl carrier protein; MT: Methyltransferase; E: Epimerase; AT: Acyltransferase; ACP: Acyl carrier protein; KS: Ketosynthase; KR: Ketoreductase; DH: Dehydratase; ER: Enoyl reductase; TE: Thioesterase. Structures of NRPS and PKS products in freshwater cyanobacteria. A) Synthesis of the