Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• Aromatic prenyltransferases (PTases) are enzymes that catalyze Friedel–Crafts reactions between aromatic compounds and isoprenoid diphosphates. In hapalindole biosynthesis, the aromatic PTases AmbP1 and AmbP3 exhibit surprisingly plastic selectivities. AmbP1 not only transfers the geranyl group on the C-3

• biosyntheses, two research groups independently sequenced the genome of a cyanobacterium, Fischerella ambigua UTEX 1903, and performed a biosynthetic study [18][19]. Among the identified biosynthetic enzymes, the major contributors of the structural diversity are two prenyltransferases (AmbP1 and AmbP3) [18

• , are well conserved among the ABBA family enzymes, but R46 is only conserved between AmbP1 and AmbP3, and Y227 is only conserved among AmbP1, AmbP3, and CloQ [28] (Figure 6), indicating that the structures for the pyrophosphate binding pockets in AmbP1 and AmbP3 are slightly different from those of the

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• [23]. An analysis of the analogous enzymes in micacocidin [13], yersiniabactin [16], and enantio-pyochelin [24] biosynthesis confirmed that the presence or absence of this feature allows a reliable prediction of the stereochemistry in this position (Table S1, Supporting Information File 1). In every

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• to possess physicochemical and biological features different from those of the two separate molecular entities [57][58]. Despite nature does not provide examples of steroid–peptide conjugates, chemists have produced such conjugates to be employed as protease-like artificial enzymes [59] as mimics of

Mechanochemical amorphization of chitin: impact of apparatus material on performance and contamination

• Thomas Di Nardo and
• Audrey Moores

Beilstein J. Org. Chem. 2019, 15, 1217–1225, doi:10.3762/bjoc.15.119

• lies outside of the milling chamber where sample can pass in and out for continuous monitoring [48]. This allows for varying milling media with the benefit of in situ measurements. For some processes like reactive aging with enzymes [22], polytetrafluoroethylene (PTFE) jars were preferred over

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• synthase from S. coelicolor [18]. The second most widely distributed terpene synthases are the 2-MIB synthases (Figure 1). As discussed below, the phylogenetic analysis of 2-MIB synthases classifies these enzymes into three different groups. This distribution is also indicated in Figure 1 (white, light

• -dependent methyl transferases were found forming a cluster together with the 2-MIB synthase in several Streptomyces species [26][27]. Besides the C-terminal domain typical of class I terpene synthases, these enzymes contain an additional proline-rich N-terminal domain that appears to be disordered in the

• 3 [30]. These enzymes are the most widespread sesquiterpene synthases in bacteria, and their coding genes are present in the genomes of more than 100 of the sequenced Streptomyces species [13]. Interestingly, epi-isozizaene synthases are only present in members of one clade (indicated as the green

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• cavity [71]. Conclusion The binding pockets within enzymes, lectins, and related protein receptors are amphiphilic; that is, they contain a mixture of polar and non-polar functional groups. The macrocyclic tetralactams highlighted in this review are biomimetic in that they are synthetic host molecules

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• or multiple compounds, are terpene synthases (TSs). These enzymes are able to guide complex cascade reactions from structurally simple oligoprenyl diphosphates to often complex, polycyclic products [4][5][6] circumventing the low selectivity observed for carbocationic reactions by a defined active

• -site architecture. Although these enzymes are mostly highlighted for their great product selectivity, TSs producing only one compound are by far not the general case. Mostly, the main product is accompanied by several side products. Prominent examples are the TS identified from the plant Medicago

• elucidate every stereochemical detail of a terpene cyclisation mechanism for a comprehensive picture of the complex reactions, these amazing enzymes are able to catalyse. Total ion chromatograms of hexane extracts from the incubations of HcS with A) FPP, B) GPP and C) GGPP. Peak numbering refers to the

New terpenoids from the fermentation broth of the edible mushroom Cyclocybe aegerita

• Frank Surup,
• Florian Hennicke,
• Nadine Sella,
• Maria Stroot,
• Steffen Bernecker,
• Sebastian Pfütze,
• Marc Stadler and
• Martin Rühl

Beilstein J. Org. Chem. 2019, 15, 1000–1007, doi:10.3762/bjoc.15.98

• in O. olearius [17], Stereum hirsutum [19] and Diaporthe sp. [20] the illudin precursor Δ6-protoilludene undergoes subsequent reactions catalyzed by enzymes, whose genes cluster with the Δ6-protoilludene synthase. Nevertheless, evidence is still missing. In C. aegerita, Δ6-protoilludene is seemingly

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• chemistry reactions, as it relies on soft force [97][98] or non-covalent interactions [2] such as hydrogen bonding [99], cation–π [100][101][102], anion–π [103], hydrophobic effect [104][105], halogen bonding [106][107][108][109], etc. As enzymes are structurally complex entities and are difficult to modify

• , supramolecular catalysis proposes a much simpler model to understand the catalytic activity of enzymes. In 2010, MacGillivray and co-workers have demonstrated the concept of “supramolecular catalysis” in a hydrogen-bond-assisted self-assembled formation of a [2 + 2]-cycloaddition product. The reaction was found

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• complexes [2]. CD derivatives have been increasingly applied in catalysis and biomimetic reactions [3][4] thanks to host–guest interactions and to the non-toxic, chiral skeleton of CDs. More specifically, CDs applied in reactions involving metal catalysis [5], organocatalysis [6] and artificial enzymes [7

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• in the catalytic action of various membrane-related enzymes, such as protein kinase C (PKC) isoforms [45]. Therefore, the development of strategies for visualization of acylglycerols in cellular environments by their fusion with fluorescent molecular labels is in high demand [46]. As a result, once

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• introduction of stereocentres to achiral starting materials by the action of enzymes. While reactions fulfilling this category are still challenging within synthetic chemistry, and methods managing to reach this goal are desperately desired, in the enzymatic world with its completely chiral environment these

• providing a defined cavity including its molecular coating together with binding and activation of the diphosphate (OPP) moiety, these enzymes convert simple achiral oligoprenyl diphosphates into often complex, polycyclic hydrocarbons or alcohols with introduction of multiple stereocentres in just one

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• selective functionalization of these cyclic oligosaccharides can remarkably improve their complexing ability and enables their application as artificial enzymes [2][3][4], chiral resolving agents [5], stimuli-responsive materials [6], molecular sensors [7] or bioactive hosts with significant emerging

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• amide [18], carbamate [19], or most recently a urea linkage [20] have been reported. Terminal alkenes are small which is beneficial for being accepted by the enzymes involved in glycan biosynthesis. However, they react only slowly in the DAinv reaction [20]. In contrast, ring-strained alkenes, such as

• results in stronger staining of soluble proteins than Ac4GlcNCp whereas Ac4GlcNCp gives a stronger cell surface staining suggests that Ac4GlcNCyoc is better accepted by the enzymes producing intracellular glycoproteins while Ac4GlcNCp is better accepted by the enzymes involved in the biosynthesis of

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

• to build synthetic metabolism. Here I discuss the current challenges and limitations in synthetic metabolic engineering and elucidate how modern day enzymology can help to build a synthetic metabolism of the future. Keywords: enzymes; in vitro biochemistry; metabolic engineering; synthetic biology

• cells to obtain a target molecule. Most of these approaches were based on the concept of metabolic engineering [10]. According to this concept, known pathways and enzymes are manipulated in such a way that a certain molecule can be produced at high purity and yield from a living bacterial cell [7]. In

• level 3 engineering efforts aim at creating new pathway solutions by mixing and matching known enzymes from different metabolic pathways, the design efforts in their most advanced form (i.e., level 4 and level 5) do not build on existing enzymes, but only consider plausible chemical transformations and

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• rounds of mutation and screening the performances of genetically-encoded enzymes. Hypothesizing that this tool may be applicable to the optimization of artificial metalloenzymes (ArMs) for olefin metathesis, a new-to-nature bioorthogonal reaction might be introduced in a biological system. ArMs result

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• nicotinamide adenine dinucleotide (NAD+, Figure 1), an intracellular redox cofactor, central to all cells’ biochemistry. Unlike its phosphorylated and reduced forms, NAD+ is also a non-redox substrate for many intra- and extracellular enzymes, participating in cellular signaling pathways and regulating post

• conditions made it possible to stop enzymatic reactions at the stage of the nicotinamide riboside formation (i. conversion of NAD+ to NMN catalyzed by pyrophosphatase and ii. conversion of NMN to NR+ catalyzed by 5′-nucleotidase) because enzymes catalyzing further degradation to Nam and nicotinic acid

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• isolation of intermediates and creating chemical diversity with high atom economy [33][34][35][36]. In the last two decades, enzymes have found a privileged place in organic chemistry by virtue of its inherent selectivity and eco-friendly reaction conditions. Such properties, among other, make them

• ][40]. Such a combination has been scarcely exploited as compared to strategies comprising transition metal catalysis and biocatalysis [41] or, in a lesser extent, organocatalysis and enzymes [42]. In this context, a versatile and robust synthesis of β-ketosulfides avoiding the use of thiols under

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• Abstract Thiamin diphosphate (ThDP)-dependent enzymes constitute a large class of enzymes that catalyze a diverse range of reactions. Many are involved in stereospecific carbon–carbon bond formation and, consequently, have found increasing interest and utility as chiral catalysts in various biocatalytic

• catalytically inactive tricyclic state. Conversely, the inhibitor binding greatly destabilized the ylide formation. Together, these observations have significant implications for the reaction kinetics of the ThDP-dependent enzymes, and, potentially, for the use of unnatural substrates in such reactions

• . Keywords: binding site; DFT; enzyme mechanism; quantum chemical calculations; ThDP-dependent; Introduction Enzymes that depend on thiamin diphosphate (ThDP, Scheme 1) can be found in a wide range of metabolic pathways. Although they are known to catalyze the formation of C–N, C–O and C–S bonds, ThDP

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• heptadecafluoroundecanoyl chloride in the presence of Et3N and catalytic DMAP in a DMF/CH2Cl2 solvent mixture (Scheme 3). Acetylation of the 4-hydroxy group provided disaccharide 10 after F-SPE purification. We planned to employ the final CS oligosaccharides in binding studies to some of the enzymes participating in the

• biosynthesis of this polymer. The presence of aromatic rings, such as the 4-methoxyphenyl group at the anomeric position, should be avoided because these groups can significantly modify the binding mode between the CS and the enzymes. For this reason, we introduced an isopropyl group in β-position of the

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• excess starting from a commercial substrate. The reaction was carried out by using different commercially available immobilized enzymes, evaluating the catalytic activity and the enantioselectivity under different experimental conditions. Re-use of the most efficient enzyme was performed both in batch

• sustainable approach to an industrial scale. Keywords: asymmetric catalysis; biotransformations; chiral amine; immobilized enzymes; ω-transaminases; Introduction Enantiomerically pure amines are important precursors to biologically active compounds with different industrial applications, including

• more sustainable method for chiral amine production [2][3][4][5]. TAs, also known as aminotransferases, are enzymes capable of transferring an amino group from an amine donor to an acceptor containing a carbonyl functionality in the presence of pyridoxal-5'-phosphate (PLP) as a cofactor and the enzymes

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

• constant for the hypothetical enzyme–substrate complex, KS [1][2]. At the time, the choice of the terms Vmax and KS was logical because the concentrations of enzymes could not be determined and even the chemical makeup of enzymes was unknown. By including the unknown enzyme concentration in the term for

• that substrate binding was at equilibrium, and was later expanded by Briggs and Haldane [3] who used the steady state approximation to include the rates of substrate and product release in defining Km according to a minimal model. A century later, we know the structures of enzymes and can accurately

• to understand how enzymes evolve to acquire new specificities. Analysis of enzyme families has revealed that members within a family share a common catalytic core and a variable loop domain that closes over the substrate and confers substrate specificity [16][17]. Moreover, specificity could be

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• synthesis, where enzymes of thermophilic microorganisms Thermus thermophilus HB27 (phosphoribosylpyrophosphate synthetase – PRPPS and adenine phosphoribosyltransferase – APRT) and Thermus sp. 2.9 (ribokinase – RK) carry out successive transformations of ribose and adenine heterocyclic bases into the

• the preparation of nucleosides and nucleotides due to the regio- and stereospecificity of enzymes [4][10][11], performing metabolic transformations of substrates. Phosphoribosyltransferases are increasingly being widely used as key enzymes in multi-enzymatic systems [2]. The substrate specificity of

• were verified by sequencing. The codone GGG→AGG substitution corresponding to amino-acid Arg27Gly replacement was found in the gene encoding the TthHPRT. The screening of available producer strains was performed to find strains, which produce target enzymes in soluble form. The resulting strains E

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• ] and the didehydrohydroxamate TSA (2) [24], display useful anticancer properties through inhibition of histone deacetylase enzymes (HDAc) and are used as FDA-approved drugs. Similarly, the cyclic peptide Chap-31 (3) [25] with a terminal hydroxamic acid residue has shown promising anticancer activity

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

• structural requirements of the Pt-based compounds as an alternative to the conventional antibiotics. Such compounds could also be used synergistically with specific enzymes that degrade the biofilm matrix [46] or biofilm-dispersal agents to boost the eradication of biofilms, to provide better treatment