Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• pathways Furthermore, there are examples of the enzymatic synthesis of plant-derived pharmaceutical meroterpenoids through the heterologous expression of a combination of fungal and plant biosynthetic enzymes. The biosynthetic enzymes StbA (polyketide synthase, PKS) and StbC (prenyltransferase, PT) from

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• ]. As an alternative to the chemical synthesis of indigo, environmentally friendly biological approaches towards constructing the indigo scaffold are also being developed for nearly a century [5][6][7][8]. The biosynthetic methods include production of indigo by microorganisms and enzymatic synthesis

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• of the individually expressed domains shows a similarly rapid precipitation as domain B alone. However, some interaction between the individually expressed domains A and B can be concluded from their reduced productivity in comparison to domain B alone. Enzymatic synthesis of non-natural analogs of 2

• and 2MIBS for the enzymatic synthesis of analogs of 1. Through this approach two new homologs of 2-methylisoborneol and 2-methylenebornane could be obtained, besides an inseparable mixture of two more tenatively identified compounds. The poor conversion of GPP by 2MIBS demonstrates its strong adaption

• coupling of DMAPP and 2-Me-IPP to 2-Me-GPP, and 2MIBS for the conversion into 1. Enzymatic synthesis of analogs of 1. A) Preparation of 2 from DA-4 and IA-1, B) preparation of 3 and the inseparable mixture of 4 and 5 from DA-5 and IA-1, C) structures of 2MIBS side products 6 and 7, and D) the

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• evaluation against GMD. Keywords: alginate; chemical probe; enzymatic synthesis; GDP-mannose dehydrogenase; sugar nucleotide; Introduction The opportunistic Gram-negative pathogen, Pseudomonas aeruginosa (PA), becomes the dominant pathogen in patients suffering from cystic fibrosis (CF) and causes a

• -phosphate 17 as the sodium triethylamine salt. Overall, the synthesis of 17 was developed in 4 steps and 46% overall yield from 14. With the required C6-modified glycosyl 1-phosphates in hand, we next evaluated them as substrates for enzymatic sugar nucleotide synthesis. Enzymatic synthesis of C6-modified

• (see Figure S3 in Supporting Information File 1). Further analytical HPLC analysis for the formation of 19 from 17 after 16 h indicated a product had formed with a similar retention time to the control synthesis of 1; this was tentatively assigned as 19. Given this, we completed further enzymatic

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• linear cascade to produce the desired NTP. Figure 3b shows the reaction sequence from 5-fluorouridine-5’-monophosphate to the triphosphate in an enzymatic synthesis of an unnatural uridine nucleotide [42]. In these type of setup, the yield of the overall reaction is strongly determined by the position of

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• ][16], the details of the complex biosynthetic enzymes producing these compounds have remained enigmatic. Therefore, this review will focus on the enzymatic synthesis of endoperoxide natural products, by summarizing the recent structural and mechanistic analyses of endoperoxide formation reactions by

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• under investigation [9][10][11]. For this study, the enzymatic synthesis was chosen for its simple reaction sequence (Figure 1) and high selectivity. Different research groups already described the reaction kinetics of the epimerase and aldolase at ambient pressure [5][8]. In this study, the rate

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• produce the chiral oxathiolane precursor 68 of lamivudine (1) from a mixture of isomers, i.e., 67, the reaction occurred in a single-phase aqueous system, which may be considered a green chemistry approach. Recently, Zhang and co-workers [63] developed a one-pot enzymatic synthesis of enantiopure 1,3

• -189 (1c) showed potent anti-HIV-1 activity. The EC50 value of (±)-BCH-189 (1c) was reported to be in the range of 0.37–1.31 µM (mean 0.73 µM), and the compound was effective against HIV-1 in MT-4 cells [13]. Enantioselective enzymatic synthesis of 3TC (1) was also reported by Milton et al. [47], who

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• only small modifications, hampering the formation of unnatural polymers. Low glycosylation yields and product hydrolysis represent additional hurdles associated with enzymatic synthesis of polysaccharides [23]. With this approach, homopolymers are often obtained as non-uniform samples, because the

• overcome some limitations of the individual methods, a combination of methods is sometimes exploited. A classic example is chemoenzymatic synthesis, in which synthetic BBs are employed to direct the enzymatic synthesis towards the desired polysaccharide target. In this review, we discuss the recent efforts

• enzymatic synthesis of cellulose was reported by Kobayashi in 1991 [61]. Since then, a plethora of enzymes [62] and substrates [63] were developed, aiming to narrow the dispersion of molecular weight (MW), increase the DP, or control the molecular organization of the resulting material (Scheme 1). Enzymatic

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• individual carbon position by enzymatic synthesis [14][29][30][31][32]. Here we report on the MS fragmentation mechanisms for the bacterial compounds sestermobaraenes A, B, and C, representing the first mechanistic study of this kind for sesterterpenes. Results and Discussion Experimental basis The 25

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• substrates of the phosphorolysis of uridine, thymidine, and 1-(β-ᴅ-arabinofuranosyl)uracil (Ara-U) catalyzed by recombinant E. coli uridine (UP) and thymidine (TP) phosphorylases. α-ᴅ-Pentofuranose-1-phosphates (PF-1Pis) obtained by phosphorolysis were used in the enzymatic synthesis of nucleosides. It was

• amounts of inosine and phosphate as starting material it was found that only 10 per cent of the riboside undergoes phosphorolysis at pH 6.5” [16]. Presently, the observation made by Kalckar is one of the hot issues from a viewpoint of the development of efficient enzymatic synthesis of nucleosides

• discussed above prompted us to start the search for simple and at the same time effective methods for the enzymatic synthesis of α-ᴅ-pentofuanose-1-phosphates (PF-1Pis) as key intermediates for the synthesis of nucleosides according to Kalсkar by phosphorolysis of readily available pyrimidine and purine

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

• provides direct access to the non-acylated forms of NR+, and NMN, or even mainly α-NR+. 2.3. Enzymatic synthesis of NR Nicotinamide riboside may be prepared enzymatically from NAD+ and NMN by several procedures. Kaplan and Stolzenbach [43] proposed an enzymatic cleavage of NAD+ to NMN by using snake venom

• enzymatic synthesis of NR+ from α-D-ribose-1-phosphate and Nam by catalysis with purine nucleoside phosphorylase and sucrose phosphorylase is described in a US patent application by Velasquez et al. [46]. In the NMR experiments, the authors demonstrated the preparation of NR+ but did not isolate pure NR+. 3

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

• – ribokinase; Tth - Thermus thermophilus; 2-Сl-AMP – 9-(β-D-ribofuranosyl)-2-chloroadenine 5'-monophosphate; Allop-MP – 1-(β-D-ribofuranosyl)-pyrazolo[3,4-d]pyrimidine-4-one 5'-monophosphate A multi-enzymatic synthesis of modified adenosine -5'-monophosphates. Nucleotide synthesis using

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

• methodology of enzymatic synthesis of these particular (but mostly unstable) carbohydrate derivatives. These mutants were also developed as powerful biocatalysts for the synthesis of complex O-glycosides through the concepts of glycosynthases or thioglycosynthases [61]. S-Glycoside synthesis In retaining GHs

• and GHs begin to be well understood by the glycoscientists. Their application to the enzymatic synthesis of a great variety of O- and N-glycosides are already becoming a routine. In addition the utilization of enzymes so to obtain rarer C- and S-analogues is an emerging field restricted to few

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates

• Tyler M. M. Stack,
• William H. Johnson Jr. and
• Christian P. Whitman

Beilstein J. Org. Chem. 2017, 13, 1022–1031, doi:10.3762/bjoc.13.101

• -chloro derivative). The enzymatic synthesis relies on the actions of the 4-OT and 4-OD/E106QVPH (both from P. putida mt-2), which carry out ketonization and decarboxylation, respectively, of 3c and 3d [11]. (The 4-OD/E106QVPH retains full decarboxylase activity, but has very little hydratase activity [10

• /E106QVPH in the “one-pot” enzymatic synthesis. The stereochemical outcome of the 4-OD reaction is consistent with previous work indicating that it is not affected by the halogen [11]. In the course of the enzymatic synthesis, it was discovered that 4-OT is inactivated by 5b–d, where 5d is the most potent

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• publications are available on the enzymatic synthesis of these nucleosides. W. H. Prusoff reported on the first efficient transformation of 6-azathymine into its 2'-deoxy-D-riboside in phosphate buffer (50 mM, pH 8.0; 37 °C) in the presence of thymidine as a pentofuranose donor and washed cells or cell-free

• preparation of trans-N-deoxyribosylase from Lactobacillus helveticus NCIB 6557 [30] had been described [31]. As for an enzymatic synthesis of thioxopyrimidine nucleosides, Kalckar [32] as well as Friedkin and co-workers [33][34] disclosed the formation of 2-thiouracil riboside and 2'-deoxyriboside using 2

• investigate the enzymatic transformations of 2(4)-thioxo- and 6(5)-azapyrimidines and their nucleosides in more detail and to outline (i) the scope and limitations of the enzymatic synthesis of 2'-deoxy-β-D-ribonucleosides catalyzed by the recombinant E. coli uridine (UP; EC 2.4.2.3) and thymidine (TP; EC

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• each case, as for any multi-enzymatic synthesis, will depend on a combination of factors such as the number of enzymes to be utilised, the ease of substrate and product diffusion through the cell membrane, and the presence of unwanted background reactions. Within a well-understood cellular chassis, the

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• -trichloroethyl)malonate to give the mixed malonyl derivatives 8a and 9a, respectively, were followed either by a palladium-catalyzed hydrogenolysis of the benzyl moiety to give 8b [26], or by a selective chemical removal of 2,2,2-trichloroethanol with Zn/AcOH to give 9b [27]. c) Enzymatic synthesis of symmetric

• related to the synthesis of these compounds was that a dimer should be more bioactive than a monomer, but this was not always the case [28][29]. d) Enzymatic synthesis of hybrid dimers According to a pioneering paper Dordick linked glucose to paclitaxel with divinyl adipate in a two-step biocatalyzed

• the synthesis of “sweet silicones” by Novozyme 435-catalyzed formation of ester bonds between organosilicon carboxylic diacids and the primary OH’s of 1-O-alkyl glucopyranosides [47]. 2. Enzymatic synthesis of polyesters The interest in the biocatalyzed synthesis of polyester started at the very

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• [19]. 1-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)thymine (FMAU) [20] was used as a source of the phosphate 12a in the first enzymatic synthesis of purine 2-deoxy-2-fluoro-β-D-arabinofuranosyl nucleosides patented by Krenitsky and co-workers (Wellcome Res. Labs) [21]. The transfer of the pentofuranose

• obtained in 29 and 39% yield, respectively [19]. Previously, we have applied the MacDonald method for the synthesis of α-D-arabinofuranose-1-phosphate (Ara-1P) and showed that it is a versatile substrate for the enzymatic synthesis of both purine and pyrimidine nucleosides [22][23]. In addition, we

• a productive transition state of the base and 12a. The good substrate properties of the phosphate 12a prompted us to test it in the enzymatic synthesis of base-modified nucleosides 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aza-7-deazaguanine (4a; purine numbering) and 9-(2-deoxy-2-fluoro-β-D

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

• possessing a C-8 hydroxyl and not a C-8 acyloxyl were detected in a ∆antB mutant [38]. In vitro enzymatic synthesis showed that AntB is incredibly promiscuous and is capable of accepting a wide variety of substrates, including an alkyne-containing moiety, which has not been observed previously in the

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• , and Glu244) and the O-2 and O-3 of fructose. This figure was created using PDB File 2HK1 [38]. Synthesis of D-tagatose from D-galactose using L-arabinose isomerase. Synthesis of D-psicose from D-fructose using D-tagatose 3-epimerase/D-psicose 3-epimerase. Enzymatic synthesis of D-psicose using

• aldolase FucA. Proposed pathway of the D-sorbose synthesis from galactitol or L-glucitol. Simultaneous enzymatic synthesis of D-sorbose and D-psicose. Biosynthesis of L-tagatose. Preparative-scale synthesis of L-tagatose and L-fructose using aldolase. Biosynthesis of L-fructose. Preparative-scale synthesis

• of L-fructose using aldolase RhaD. Chemoenzymatically synthesis of 1-deoxy-L-fructose [8]. Potential enzymes (isomerases) for the bioconversion of D-psicose to D-allose. Three-step bioconversion of D-glucose to D-allose. Biosynthesis of L-glucose. Enzymatic synthesis of L-talose and D-gulose

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• unsatisfactory and the enantioselectivities were modest [20]. In recent years, inspired by the enzymatic synthesis of polyketides and fatty acids in biological systems, the enantioselective decarboxylative reactions of malonic acid half thioesters (MAHTs) have received much attention. In this regard, various

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• oligomers containing terminally and/or internally modified galactose residues were obtained, which can be used for binding studies and various other applications. Keywords: chemo-enzymatic synthesis; galactose oxidase; glycosyltransferase; LacDiNAc; poly-N-acetyllactosamine; Introduction N