Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• × 105 cells per 24 well plates in RPMI with 10% FBS. MTT Assay: The MTT assay is a colorimetric assay for evaluation of cell metabolic activity. The NADPH-dependent cellular oxidoreductases present in the living cell can reflect, under certain conditions, the cell viability. These enzymes can reduce the

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• to the corresponding amino acid via electrochemical reduction of FAD in AOx by electron mediator ADPy. It should be noted that the authors also reported the limitation of this electrochemical method in terms of substrate selectivity of the enzymes used [44]. Electrochemical asymmetric oxidation using

• potentiostatic electrolysis, styrene derivatives 143 could be transformed into their asymmetric epoxides 144 via direct electrochemical regeneration of FADH2. The authors claimed that this method is superior with respect to substitution of the complex native regeneration cycle, which consists of three enzymes

• chloroperoxidase catalyst. H2O2 generated in situ from the cathodic reduction of oxygen was proposed to be responsible for the enzyme-mediated thiol ether oxidation (Scheme 47) [82]. Vitamin B12-dependent enzymes are an exciting representative in the family of chiral inductors for electroorganic chemistry. These

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

• 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

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• activity and physiological events with light. A number of protein targets have been explored with photochromic small-molecule ligands, such as ion channels, microtubules, enzymes and GPCRs (G protein-coupled receptors) [1][10]. We focus our photopharmacology research on GPCRs [3][7][11], which constitute a

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• switching capacities and duplex formation were analyzed. Our group has recently demonstrated that photoresponsive peptides can affect the transcription of genes via inhibition of histone-modifying enzymes [37]. Repression of enzymes is achievable at nucleic acid level too. Therefore, in this project we

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

• MI614-43F2 comprises four enzymes: GGDP synthase (CotB1), a diterpene cyclase (CotB2) and two P450 cytochromes (Figure 1) [31]. The cyclization of GGDP 3 to cyclooctat-9-en-7-ol (4) is performed by the TPS CotB2. Compound 4 is further decorated with two hydroxy functions introduced by two P450

• enzymes that is widely distributed among plants, fungi and bacteria. CotB2 has evolved to convert the acyclic, achiral substrate GGDP to the 5–8–5 ring motif of cyclooctat-9-en-7-ol that contains six chiral stereocenters. Hence, CotB2 has been fine tuned to perform a highly specific regio- and

• acyclic substrate GGDP (3) is stereospecifically cyclized by CotB2 to cyclooctat-9-en-7-ol (4), with a fusicoccane 5–8–5 fused ring system. Two cytochrome P450 enzymes, CotB3 and CotB4, subsequently functionalize cyclooctat-9-en-7-ol (4) to the bioactive compound cyclooctatin (5). The bacterial diterpene

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• three types based on their amino acid sequence. Type I TPSs are metal-dependent enzymes that initiate cyclisation by the elimination of diphosphate groups from precursors and carbocation formation, and type II TPSs initiate the catalytic process by the protonation of an olefinic double bond [7]. The

• structurally diverse (poly)cyclic core skeletons [3][12]. A set of post-modification enzymes can transform core sesquiterpene skeletons into different kinds of sesquiterpenoids with potential anticancer, cytotoxic and antibiotic functions [13]. More than 121 skeleton structures derived from the sesquiterpene

• of 89.66% and 85.23% with the enzymes from the strain T. virens Gv29-8 [27] and T. reesei QM6a [28], respectively, with only predicted functions. Thereafter, an amino acid sequence alignment with several known terpene synthases showed that Tvi09626 had the typical highly conserved 128DDxxD/E

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• [27]. Then, the bifunctional P450c17 acts as a 17α-hydroxylase and 17,20-lyase to give rise to androstanes [27]. Related enzymes have not been reported from plants. We searched transcriptome data of P. peruviana for putative homologues of these enzymes [28]. The best hits only had amino acid sequence

• identities of 22–28%, indicating that no P450 enzymes of these clans exist in P. peruviana. Although enzymes with similar catalytic activity might have evolved convergently in plants, the different substitution pattern in the side chain suggests that a side-chain cleavage mechanism distinct from mammals is

• directly linked to the known withanolides 4ß-hydroxywithanolide E (1), withanolide F (5) and withanolide S [23], respectively (Figure S20, Supporting Information File 1). If the fragmentation occurred early in the biosynthesis, this would imply that several biosynthetic enzymes have to tolerate substrates

Complexation of 2,6-helic[6]arene and its derivatives with 1,1′-dimethyl-4,4′-bipyridinium salts and protonated 4,4'-bipyridinium salts: an acid–base controllable complexation

• Jing Li,
• Qiang Shi,
• Ying Han and
• Chuan-Feng Chen

Beilstein J. Org. Chem. 2019, 15, 1795–1804, doi:10.3762/bjoc.15.173

• are also the epitome of complex-binding pockets of enzymes [3]. Macrocyclic arenes including calixarenes [4][5], resorcinarenes [6], cyclotriveratrylenes [7][8], pillararenes [9], biphen[n]arenes [10] and others [11][12] are all composed of hydroxy-substituted aromatic rings bridged by methylene or

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