Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• showed that the strain expressing NcALD8 could produce 4.42 mg/L of crocetin (1) [109]. In addition to the de novo biosynthesis of crocetin (1), Shan et al. reported the biotransformation of crocetin (1) from zeaxanthin (7). When the 3-OH-β-apo-8'-carotenoic acid (3-HACA) byproduct was eliminated by

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

• macrolactones. Using engineered variants of S. venezuelae ATCC 15439 designated strains DHS200141 [71] and YJ11242 [72], 24 and 25 were transformed to the corresponding macrolides through whole cell biotransformation to append ᴅ-desosamine and perform C–H oxidation(s) by the PikC monooxygenase (Scheme 6b). In

• contrast to Kang’s chemical synthesis route, this biotransformation provided a more efficient and productive strategy for the desoaminylation of macrolide aglycones. Combining in vitro and in vivo enzymatic reactions together, this chemoenzymatic platform exhibits the potential to access a broader range of

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• . However, our understanding of the dimerization enzymes involved in this biotransformation is still limited compared to the numerous reported dimeric natural products. Here, we report the characterization of three new isoflavone dimers from Streptomyces cattleya cultured on an isoflavone-containing agar

• , which extends the insights into P450-mediated biaryl coupling reactions in biosynthesis. Keywords: biaryl coupling; cytochrome P450; dimerization; isoflavone; natural product; Introduction Dimerization is a ubiquitous biotransformation in nature. Almost all forms of life, including bacteria, fungi

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• rotation signal ( +169.6 (c 0.12, CHCl3) for (+)-1, −186.0 (c 6.30, CHCl3) for (−)-1), were almost identical to those of 2β-hydroxyaromadendr-1(10)-en-9-one [(−)-1] [19], namely (1aR,5R,7R,7aS,7bR)-1,1a,2,5,6,7,7a,7b-octahydro-5-hydroxy-1,1,4,7-tetramethyl-3H-cycloprop[e]azulen-3-one, a biotransformation

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• have presented the results of the synthesis of the 9,11-secosteroid carbon skeleton by using the designed whole-cell biotransformation of natural steroids with a genetically engineered biocatalyst. The enzymatic oxidation of cortisol derivatives is completely stereo- and regioselective, affording only

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• biosynthesis and biodegradation of fluorinated organic compounds is also described. Keywords: biotransformation; chemical biology; fluorine; 19F NMR; probes; protein structure; Introduction Although fluorine is abundant in the environment, it is not a nutrient nor is it a feature of biochemistry for most

• examples demonstrate that 19F NMR offers a suitable and non-perturbing approach by which to access detailed structural information of complex DNA and RNA folding topologies and sophisticated supramolecular assemblies. Metabolism studies Biotransformation of fluorinated xenobiotics Fluorine is present in a

• degree. In our previous review [4], we highlighted 19F NMR’s usefulness in following the biodegradation of compounds such as fluorophenols and fluorobenzoates. The technique has since been applied to monitor the biotransformation/biodegradation of fluorinated drugs such as flurbiprofen [105], and 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

• -phenylcyclopropanecarboxylic acid 82 and amide 83 in both enantiomeric forms (Scheme 33). The biotransformation of the gem-difluorocyclopropane 81 produced good results for both the rate and yield. The (1S,3S)-acid 82 and (1R,3R)-amide 83 were synthesized in 52% yield with 53% ee and 32% yield with >99% ee, respectively. The

• biotransformation of gem-difluorocyclopropanecarboxamide (±)-83 (Scheme 34) occurred rapidly and under mild conditions to give (1R,3R)-amide 83 (46% yield, >99% ee) and (1S,3S)-acid 82 (51% yield, 87 % ee). Enantioselective hydrogenation of difluorocyclopropenes: Recently, Mikami and co-workers reported the

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• biocompatibility while remaining fluorescent. Keywords: ball milling; boronic ester; dextran; bodipy; nanoparticles; Introduction In the last few decades, mechanochemistry has gathered a great deal of attention and a lot of efforts have been focused on its use in organic synthesis, catalysis, biotransformation

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• size (volume), solvation (dipole moment), and chemical reactivity (hardness; probably related to a minor metabolic biotransformation). These descriptors can be associated with the better pharmacokinetic profile of the derivatives 3 and 4 by oral administration. Molecular docking As a second

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• natural biotransformation (67→68) and olfactory property of tetrahydrofuran 70 [39]. Individual components of the complex Iso E Super® mixture. Top fragrances with regard to their volume percentage (listed down to about 20%; the large number of perfumes with lower percentages are not listed) of Iso E

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• addition of 1 to the cultures represent a combination of auto-induction of AQ synthesis by HHQ, and biotransformation of HHQ to PQS. However, HHQ is not a biosynthetic precursor of HQNO. Means and standard errors of five biological replicates are shown. One-way ANOVA was used for statistical analysis, and

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

• times and lower costs for the chemical and enzymatic reactions involved. Keywords: bile acids; biotransformation; hydroxysteroid dehydrogenases; production process; UDCA; Introduction Ursodeoxycholic acid (UDCA), is applied in the pharmaceutical industry (Figure 1) [1]. As reported in several papers

• . An approach that bears great promise is the biotransformation with non-pathogenic, easy-to-manage microorganisms, and their enzymes. Several chemical, chemoenzymatic and enzymatic routes have been proposed for the production of UDCA. In view of sustainability, instead of pursuing a step-wise approach

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• , Shanghai Normal University, Shanghai, P. R. China Lehrstuhl für Pharmazeutische Biologie, Institut für Pharmazie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany Centre of Biotransformation and Biocatalysis, Institute of Microbiology, Czech Academy of Sciences, Videnska 1083

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

• [39]. Carboxysomal proteins have also been expressed in E. coli yielding a highly organised structure [41]. Use of carboxysomes for micro-compartmentalisation of CO2 biotransformation may therefore become a viable strategy in a range of synthetic biology applications, because not only CO2-transforming

• into products of interest [149]. Prospects and challenges for future biotechnological applications In order for CO2 biotransformation to target a broad range of commodity chemicals, the CO2-fixing enzymes must be used as part of multi-enzymatic cascades that convert CO2 through multiple steps [111][150

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

• utilization pathway; whole-cell biotransformation; Introduction Bioreductions represent a sustainable strategy to obtain enantiopure molecules which serve as chiral building blocks for fine chemicals and drugs [1][2]. Such reactions are catalyzed by oxidoreductases, which mainly depend on nicotinamide

• Δdas2 background were investigated under optimized conditions in shake flasks. To avoid differences in the amount of cells employed in the biotransformation and to obtain higher product yields, cells corresponding to 3000 OD600 units were harvested 12 h after the first methanol induction and resuspended

• in 50 mL of buffered minimal medium before the conversions were started by the addition of substrate. During the first two hours of the whole-cell biotransformation, the conversions obtained with each of the strains were in the same order of magnitude (see Figure 4B). After longer reaction times

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

• hydroxylations. Keywords: active site mutagenesis; biotransformation; C–H activation; cytochrome P450cam monooxygenase; hydroxylation; Introduction Selective C–H activation and oxyfunctionalisation of hydrocarbons offers a route to chiral alcohols and other industrially important synthetic building blocks from

• 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

• and ee’s obtained in biotransformation experiments with substrates 5–8 with the parent P450cam[Tyr96Phe]-RhFRed and indigo positive variants from library III (Met184/Thr185).a Supporting Information Supporting Information File 312: General experimental information and procedures. Acknowledgements We

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

• ), substrate-to-acyl group donor molar ratio (1:30), and the temperature (25 °C). Finally, after finding optimal biotransformation conditions in a mg-scale, we have successfully performed the reaction in gram- and multigram-scales providing sufficient amounts of optically active alcohol intermediates (S)-(+)-5

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• desepoxy-derivatives 24b–d were encountered. Finally, also the propargyl-modified proansamitocin 24e and two truncated derivatives 24f and 24g were obtained. We had observed this unprecendeted defunctionalization at C7 in proansamitocin and the possible biotransformation before for the mutasynthon 5-chloro

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

• rearranged oxidation products 9a and 9b were each supplemented to cultures of A. pretiosum HGF073, new products were formed. While the carbamoylated derivative 12 resulting from biotransformation of alcohol 9b can be attributed to the activity of the carbamoyltransferase Asm21, thereby providing an

• carbamoylated product could be isolated after the biotransformation of compound 9a, indicating an efficient transformation of the suspected carbamoylated intermediate to the final product 13a. All (pro)ansamitocin derivatives fully characterized by NMR were also subjected to in vitro biological testing with

• – Braintree Scientific BS-9000-8 syringe pump with Upchurch Scientific high-purity Teflon® PFA tubing (1/16” OD, 0.1” ID) and Tefzel® connectors. Biotransformation of the proansamitocin derivatives 9a, 9b and 12 was carried out by supplementing a production culture of A. pretiosum HGF073 (45 mL final volume

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

• phenyl ring. Analysis of the products arising from the biotransformation with p-methyl 3b and the p-chloro 3c derivatives revealed that the bacterium was capable of catalysing hydroxylation selectively in the C5-position, providing the C5-axial isomers 4b and 4c and C5-equitorial hydroxylated isomers 5b

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

• -called “liquid gas” n-butane (boiling point: −0.5 °C), at a low starting temperature, which was chosen in the range of −5 to 8 °C. For the biotransformation of this liquid gas the following experimental procedure was carried out: First, all components required for the reaction (in a particular solvent

• lacking high-pressure equipment. A current challenge, addressed in our laboratories, is the further improvement of process efficiency and volumetric productivity of this enzymatic oxidation process. In addition, studies of enzyme stability during this biotransformation process are planned as future work

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• approaches towards libraries of new compounds or for rational biotransformation of existing leading compounds. This review gives an overview of the current trends in cyanobacterial natural-product research, with a special emphasis on the biosynthetic enzymes. Review Biosynthesis of peptides and polyketides

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

• mutation into our P450cam-RhFRed fused system made the whole cell biotransformation of diphenylmethane as a substrate possible (4 mL reaction in a 15 mL Falcon tube) with a GC–MS yield of 58% of 4-hydroxydiphenylmethane after 48 h (Scheme 1). In order to improve screening throughput, we investigated the

• whole cell biotransformation of diphenylmethane with P450cam(Y96A)-RhFRed in multiwell plates (24, 48 and 96) with different reaction volumes (0.5 mL, 1 mL and 2 mL). The biotransformation carried out in a 48-well plate with a reaction volume of 1 mL was found to give a similar conversion to the 4 mL

• turned out to be the most efficient for the epoxidation of the tetrahydropyridine ring, with substrate 7b epoxidised to 8b in 73% conversion. Racemic epoxide 8b was synthesised to confirm the structure of the biotransformation product and to determine the enantiomeric excess. This was found to be 18% for

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

• indispensable part of industrial biotechnology, and are used in the production of a broad range of bulk and fine chemicals [6]. When a microbial multistep biotransformation is carried out in continuous flow it might formally also be considered as a fourth-generation enzymatic process according to the above

• continuous epoxidation of 1,7-octadiene (70) to (R)-7-epoxyoctene (72) by a strain of Pseudomonas oleovorans growing on heptane (71) (Scheme 23) [51]. In a continuous operation, with regard to the aqueous phase, substrates for both growth and biotransformation were supplied in the gas phase from a reservoir

A simple route for renewable nano- sized arjunolic and asiatic acids and self- assembly of arjuna- bromolactone

• Braja G. Bag,
• Partha P. Dey,
• Shaishab K. Dinda,
• William S. Sheldrick and
• Iris M. Oppel

Beilstein J. Org. Chem. 2008, 4, No. 24, doi:10.3762/bjoc.4.24

• acid, as a minor component having a close structural resemblance [12][13]. Biotransformation of the ursane to the oleanane skeleton has recently been reported [14], but no simple method for the separation of the two triterpenic acids is known [15]. Herein we report a simple method for separation the