Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• step counts, increasing yields, and minimizing waste generation as they couple different biotransformations in sequential reactions. Although TE-mediated chemoenzymatic synthesis is becoming a prospective strategy, many challenges still need to be resolved, such as limited reaction solvents, enzyme

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• reactions (e.g., hydrolysis, esterification, oxidation) might be due to the isolation conditions or they could be attributed to unspecific enzymatic biotransformations. For compound 1, no spontaneous conversion to the ester 2 was observed, even after storage in methanol for two months. In contrast, the

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• smooth hydrolysis. Wang et al. reported the enantioselective biotransformations of geminally difluorinated cyclopropanecarbonitriles and amides in 2004 [77]. They transformed gem-difluorocyclopropane derivatives with the help of a soil microorganism, Rhodococcus sp. AJ270, which provided a very effective

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• . Biotransformations and extraction conditions Culture media was purchased from Sigma-Aldrich. Each thioether (5–10 mg) was dissolved in DMF (50 µL) and inoculated into cultures of C. elegans. The cultures were incubated at 28 °C and 180 rpm for 72 h. Blank experiments were carried out in the absence of C. elegans

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

• 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

• by using resolution of racemic mixtures, preparation from chiral precursors or asymmetric synthesis from prochiral compounds [20][21][22]. In contrast, only few examples have been published on the synthesis of this molecule through biotransformations [23][24]. In these procedures TAs are used in

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• several research groups to focus their attention on the development of biotransformations with non-pathogenic, easy-to-manage microorganisms, and their enzymes. In particular, the enzymatic reactions involved are selective hydrolysis, epimerization of the hydroxy functions (by oxidation and subsequent

• ][67][68][69][70]. Examples of processes for the selective oxidation of bile acids, their salts or derivatives were patented [71][72]. In addition to these reported biotransformations, many additional 7α-HSDHs have been discovered and reported over the past years. About 500 entries can be found in

Engineering Pichia pastoris for improved NADH regeneration: A novel chassis strain for whole-cell catalysis

• Martina Geier,
• Christoph Brandner,
• Gernot A. Strohmeier,
• Mélanie Hall,
• Franz S. Hartner and
• Anton Glieder

Beilstein J. Org. Chem. 2015, 11, 1741–1748, doi:10.3762/bjoc.11.190

• bottleneck for an efficient cofactor recycling via the dissimilatory pathway, significantly improved the production rates of NADH-dependent whole-cell biotransformations. In contrast, the present study focuses on redirecting the flux in the MUT pathway by disrupting the assimilation pathway. Thus, the co

• -substrate methanol should be exclusively redirected to cofactor regeneration in theory, increasing the available NADH concentration in whole-cell biotransformations, while cells should not be able to grow any more if methanol is the sole carbon source. Results and Discussion Construction of knock-out

• P. pastoris strain. These findings are of importance for the use of the knock-out strains in whole-cell processes, as impairments in recombinant protein production, i.e., the production of the actual biocatalyst, would reduce its applicability. NADH-dependent biotransformations performed in knock

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• and the para-brominated derivative 7 were screened in liquid whole cell biotransformations (Tables S15–S21, Supporting Information File 1). Initially, indigo positive variants were combined from each library, with a roughly equal size of 5–8 variants per pool [33]. This pooling strategy allowed us to

• decided not to normalise enzyme activity to expression levels in subsequent activity studies. Biotransformation reactions with library pools Biotransformations with pooled libraries and ethylbenzene (5) provided the average yield of alcohols (R,S)-9 up to 10%, which is comparable to previously published

• acknowledge support from the Centre of Excellence for Biocatalysis, Biotransformations and Biocatalytic Manufacture (CoEBio3, to PPK), the FP7-PEOPLE-2011-ITN under grant agreement no. 289217 (P4fifty, to AE), the Innovative Medicines Initiative Joint Undertaking under the grant agreement no. 115360 (Chemical

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• , classical chemical manufacturing technologies are increasingly displaced by pure biotechnological processes or biotransformations coupled with chemical operations [4][5][6][7][8][9][10]. The main advantages of these impactful techniques are high substrate specificity as well as regio- and stereoselectivity

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• Information File 102: Complete experimental procedures and characterization data. Acknowledgements The project was co-financed by The European Regional Development Fund under The Innovative Economy Operational Programme 2007–2013: “Biotransformations for Pharmaceutical and Cosmetic Industry” POIG.01.03.01-00

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

Regio- and stereoselective oxidation of unactivated C–H bonds with Rhodococcus rhodochrous

• Elaine O’Reilly,
• Suzanne J. Aitken,
• Gideon Grogan,
• Paul P. Kelly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 496–500, doi:10.3762/bjoc.8.56

• influencing the regioselectivity. Transformation of THF ether derivatives The ability of the organism to catalyse the selective hydroxylation of the THP series 3b–d, prompted us to investigate the biotransformations of the corresponding racemic tetrahydrofuran (THF) compounds 9a–d. The results, shown in

Biocatalytic hydroxylation of n-butane with in situ cofactor regeneration at low temperature and under normal pressure

• Svenja Staudt,
• Christina A. Müller,
• Jan Marienhagen,
• Christian Böing,
• Stefan Buchholz,
• Ulrich Schwaneberg and
• Harald Gröger

Beilstein J. Org. Chem. 2012, 8, 186–191, doi:10.3762/bjoc.8.20

• conditions, was developed. The resulting 2-butanol was obtained as the only regioisomer, at a product concentration of 0.16 g/L. Keywords: biotransformations; cofactor regeneration; green chemistry; hydroxylation; P450-monooxygenase; Introduction The (regioselective) oxidative functionalization of

Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases

• Christian Klein and
• Wolfgang Hüttel

Beilstein J. Org. Chem. 2011, 7, 1643–1647, doi:10.3762/bjoc.7.193

• production of tertiary alcohols. Both enzymes investigated afford only a single product selectively and, in the case of cis-P4H, the activity was comparable to that with the native substrate. Moreover, proline hydroxylases can be applied for whole cell biotransformations on a preparative scale. Even though

Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope

• Aélig Robin,
• Valentin Köhler,
• Alison Jones,
• Afruja Ali,
• Paul P. Kelly,
• Elaine O'Reilly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2011, 7, 1494–1498, doi:10.3762/bjoc.7.173

• with nonfused P450cam. Initially, the microtitre-plate system was optimised and shown to give similar yields to our previously reported biotransformations. The three fused P450cam-RhFRed variants were screened against a panel of substrates, which were selected on the basis of the potential application

• ), after 24 h, of substrates 1, 3, 5, and, after 48 h, of substrates 7, 11, 13 and 15 with P450cam-RhFRed mutants in 48-well plate biotransformations. Supporting Information The Supporting Information features the full experimental procedures, characterisation of the synthesised, previously unknown

• compounds, GC–MS traces of the biotransformation reactions and the MS traces of the corresponding starting materials. Supporting Information File 196: Experimental part and GC–MS traces. Acknowledgements We wish to thank the Centre of Excellence for Biocatalysis, Biotransformations and Biocatalytic

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• field and which can be used for the classification of existing biotransformations. One of these principles is that a single reaction step of a given metabolic pathway proceeds in a very specific manner due to the intrinsically high chemo-, regio- and stereoselectivity of the enzyme catalyzing this step

• . This principle is the soul of applied biocatalysis and has already been widely exploited in the chemical industry for decades in the production of chemicals by enzymatic processes [4][5][6]. Biotransformations solely based on this principle, i.e., “single-reaction–single-enzyme” systems, may be

• classified as first-generation enzymatic processes (Figure 2, I), which historically were the first to be applied in the chemical industry and till now remain the most abundant among industrial biotransformations. The second biological principle states that cell metabolism is a continuous process. Every