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

• (37–40), though only diterpenes were observed in the culture headspace of the wild type producer (Figure 9a) [118]. These examples suggest a remarkable degree of plasticity of TC active sites in order to direct the intermediate to different trajectories and accommodate substrates with variable lengths

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

• ). CotB2 is arranged as a homo-dimer in crystallo [36][38] and it was demonstrated that CotB2 exists as a homo-dimer in solution as well [38]. The two active sites of CotB2 are arranged in an antiparallel fashion, resembling the arrangement initially observed for the monoterpene (+)-bornyl diphosphate

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• methods that succeeded in creating active sites of remarkable promiscuous activities in the scaffold of existing enzymes [42]. Such computationally-created “catalytically diverse active sites” could be further developed towards a new activity through directed evolution. Without any question, screening

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• stage of the reaction when Ru–polymer carbene active sites are formed as a result of the catalyst–polymer interaction. The decrease in Mn is observed during the first 1–2 hours and then it remains nearly unchanged [84]. The molecular mass of the resulting multiblock copolymer decreases with increasing

New standards for collecting and fitting steady state kinetic data

• Kenneth A. Johnson

Beilstein J. Org. Chem. 2019, 15, 16–29, doi:10.3762/bjoc.15.2

• concentration of active sites. There are significant systematic errors in measurements of protein concentrations using dye-binding assays or by absorbance measurements, and the fraction of protein that is active is not known without direct measurement. For these reasons, it is important to perform an active

• site titration to establish the concentration of active sites. One method is isothermal titration calorimetry relying on the heat change upon binding of a substrate analog. Because the method is relatively insensitive it requires high concentrations of protein (usually μM) so the stoichiometry is easy

• concentration of active sites under favorable conditions [15]. In any event, kinetic data should be normalized by dividing the rate by the concentration of enzyme active sites, and the basis for estimating enzyme concentration should be clearly stated. It is no longer acceptable to report enzyme specific

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• pentiptycenyl side of the NHC ligand compared to the other less hindered side determines two differently accessible active sites around the metal and different rates of monomer incorporation, thus dominating the selectivity in the formation of alternating copolymers. The nature of the alkyl group also plays a

MoO₃ on zeolites MCM-22, MCM-56 and 2D-MFI as catalysts for 1-octene metathesis

• Hynek Balcar,
• Martin Kubů,
• Naděžda Žilková and
• Mariya Shamzhy

Beilstein J. Org. Chem. 2018, 14, 2931–2939, doi:10.3762/bjoc.14.272

• . Moreover, for related system based on tungsten oxide in zeolite, it was suggested using high resolution STEM that Brønsted acid sites in proximity to metathesis active sites facilitate olefin adsorption and metallocycle formation [29]. Such mechanism may be effective also for Mo catalysts. The decrease in

• ) in accord with poor MoO3 spreading (see Figure 1D). Despite the high acidity of the support, a poor accessibility of relevant surface OH groups during the thermal spreading process and a poor accessibility of possible active sites by substrate molecule during metathesis may cause 6MoO3/HZSM-5(25) to

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• before use in the reaction. This causes that the tendency of adsorption of PFAD on active sites was decreased and consequently the catalyst will not be deactivated. A covalently grafting modified nanoscaled diamond powder with 1,3-propanesultone (Scheme 26) 138 exhibited excellent catalytic activity for

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• in (S)-nicotine to form N-methylmyosmine. The recent evidence that the product of the oxidation of 6-hydroxynicotine by LHNO and DHNO arises from oxidation of a carbon–nitrogen bond [18][24] and the similarity of the active sites of LHNO and NicA2 to that of MAO makes it much more likely that the

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• factor that significantly affects whether an enzyme-free primer extension reaction occurs in high yield or not is the strength of the template effect. Unlike the reactions that are catalyzed by polymerases, purely chemical primer extension reactions are not facilitated by the active sites of enzymes

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• the reaction between a phosphorothioate derivative and 2-bromo-4’-hydroxyacetophenone to produce a phosphate protected with a thioether-enol phosphotriester, phenol substituted (TEEP, Scheme 19) [77]. The TEEP modification was introduced into “active sites” of 8–17 and 10–23 DNAzymes with good yields

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• where both axial active sites of the catalyst are inaccessible for further interaction with diazoesters 2. To verify this assumption, a separate experiment was performed by the example of dimethyl diazomalonate (2a) decomposition with the obtained Rh-complex 6e. And it was demonstrated that under these

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• and achiral oligoprenyl diphosphates in just one enzymatic step into a remarkable diversity of usually polycyclic structurally complex lipophilic terpenes with multiple stereogenic centres. In their active sites type I terpene synthases contain the highly conserved aspartate-rich motif DDXX(X)(D,E

Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded silver nanoparticles for catalytic reduction

• Qing Yin,
• Qi Chen,
• Li-Can Lu and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 1212–1221, doi:10.3762/bjoc.13.120

• molecules into the holes with the catalyst active sites [38][39]. Therefore, it is of great interest to improve the catalytic efficiency by encapsulating the nanocatalyst in a porous organic polymer. Keeping these issues in mind, three novel sugar-based porous organic polymers SugPOP-1–3 were designed and

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• rather than in enclosed chambers, as found in fungal FAS. An approximate calculation from the dimensions of the fungal FAS (barrel structure abstracted as cylinder and considering six full sets of active sites per barrel) accounts for a virtual concentration of 1.8 mM of active sites. An analogous

• consideration for animal FAS (again abstracted as spanning a cylindrical reaction space, two full sets of active sites) gives a virtual active site concentration of 1.2 mM. Accordingly, both scaffolds of FA type I synthesis facilitate reactions at high virtual concentration of enzymatic domains. PKS

• of an E. coli cell of 2.5 µm [3][22], copy numbers account for molar concentrations of about 0.007 to 0.016 mM. Substrate shuttling FA and PK syntheses generally rely on ACP that shuttles substrates and intermediates as covalently bound cargo between active sites [23]. In FAS and PKS (type I

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• compounds. They have a specific odour and often used as gas odorants in many industrial applications [1][2]. They occur as flavouring compounds in several fruits and spices and are found in a variety of enzymes at their active sites [3]. Thiols are produced by the wood-pulping industry, manure & sewer

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• Lindlar-type catalysts, consisting in relatively high amounts of Pd (5 wt %) and Pb (2–3%) deposited onto CaCO3 [8][9], whose active sites nature is not fully characterized yet [10][11]. Besides the use of toxic lead, satisfactory catalyst performances often require a careful control of the hydrogen

• clogging, active sites accessibility, mass transfer limitations, and lack of reproducibility. Additional stabilization of MNP can be also achieved either by: the “electrostatic” effect of charged functional groups grafted to the support, a common strategy in gel-type resins (e.g., sulfonic resins) [93

• ]; the strong metal–support interactions, particularly for inorganic oxide materials, e.g., TiO2 [94][95]. Besides contributing to catalyst resistance by hampering the loss and the size increase of active sites, MNP stabilization is a key factor to limit the amount of metal leached in solution, an issue

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

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

• with the conserved Leu. In the alternative proposal [62], the direction of reduction is controlled by a divergent degree of ordering within the active sites of A- and B-type domains. In A-type KRs, cofactor binding generates a well-organized and catalysis-ready active site, in which a key residue (Met

• -oxopentanoate to an ACP, has not been tested)). In any case, these data encouraged the view that mutation of a few key residues in the KR active sites might be used to alter reduction stereochemistry. Site-directed mutagenesis can indeed modify the stereochemical outcome of ketoreduction, at least in vitro

• -methylacetoacetate) showed this reaction to be rapid at room temperature (t1/2 = 4.7 min) [82]. Thus, during polyketide biosynthesis, there must be some mechanism to protect the intermediate from spontaneous epimerization following chain extension, both as it is passed between the KS and KR active sites and within

Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• modification or addition of a functional group [13]. Controlled degradation – degradation and crosslinking of polymers to produce a product with controlled molecular weight distribution. This results in a higher number of active sites that can later be used for grafting [13]. Reactive blending – this involves

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• motives [1][2]. Selected adenines in their active sites have been discussed to participate in acid base catalysis, thereby contributing to accelerate the specific phosphodiester cleavage of these nucleolytic ribozymes. Concerning the twister ribozyme, structural analyses suggest that an adenine N3 atom

Radical polymerization by a supramolecular catalyst: cyclodextrin with a RAFT reagent

• Kohei Koyanagi,
• Yoshinori Takashima,
• Takashi Nakamura,
• Hiroyasu Yamaguchi and
• Akira Harada

Beilstein J. Org. Chem. 2016, 12, 2495–2502, doi:10.3762/bjoc.12.244

• sites and catalytic active sites have been designed for polymerization reactions, relatively few reports have described a catalytic design in which the catalytic active site does not leave the CD monomer recognition site during the growing step. In a previous design of radical initiators with CDs, the

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• and selectivity is the special confinement of the reactants and the presence of catalytic active sites, [15][16] by use of microporous materials doped with metals. While pore dimensions and topology of the microporous materials can affect the selectivity of the reaction, their activity can be strongly

Silica-supported sulfonic acids as recyclable catalyst for esterification of levulinic acid with stoichiometric amounts of alcohols

• Raimondo Maggi,
• N. Raveendran Shiju,
• Veronica Santacroce,
• Giovanni Maestri,
• Franca Bigi and
• Gadi Rothenberg

Beilstein J. Org. Chem. 2016, 12, 2173–2180, doi:10.3762/bjoc.12.207

• catalysts operate under mild conditions and give good conversion and selectivity with stoichiometric amounts of alcohols. The sulfonic acid groups are tethered to the support using organic tethers. These tethers may help in preventing the deactivation of the active sites in the presence of water. Keywords

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• extended steric hindrance over the catalytically active sites, eroded the catalytic activity and diastereocontrol (Table 1, entry 6). These observations demonstrated the superior capability of 1c in facilitating this stereoselective Mannich-type transformation, for which the loading was reduced to 1 mol

Cross-linked cyclodextrin-based material for treatment of metals and organic substances present in industrial discharge waters

• Élise Euvrard,
• Nadia Morin-Crini,
• Coline Druart,
• Justine Bugnet,
• Bernard Martel,
• Cesare Cosentino,
• Virginie Moutarlier and
• Grégorio Crini

Beilstein J. Org. Chem. 2016, 12, 1826–1838, doi:10.3762/bjoc.12.172

• to the active sites [22][23][24][25]. These observations were confirmed by the tests conducted in SS in the presence of calcium. An increase of polymer concentration in DWs (10 g·L−1 instead of 2 g·L−1) yielded better results in terms of removal efficiency for all metals. However, while the retention