Review
Biochemistry & Molecular Biology
Rebecca Roddan, Eve M. Carter, Benjamin Thair, Helen C. Hailes
Summary: This review highlights recent chemoenzymatic syntheses towards plant natural products and analogues, focusing on the advantages of incorporating biocatalysts into a synthetic strategy.
NATURAL PRODUCT REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Samantha P. Kelly, Vikram V. Shende, Autumn R. Flynn, Qingyun Dan, Ying Ye, Janet L. Smith, Sachiko Tsukamoto, Matthew S. Sigman, David H. Sherman
Summary: In this study, researchers aimed to develop a unified strategy for biocatalytic construction of prenylated DKP indole alkaloids. By identifying and characterizing a substrate-permissive C2 reverse prenyltransferase (PT) NotF, they found that NotF has a significantly broad substrate scope and strong reaction selectivity. Through the conversion of 30 different structurally differentiated substances, they identified key factors that govern the rate of NotF-catalyzed prenyltransfer and developed an engineering strategy to improve substrate turnover. Finally, they successfully demonstrated the one-pot synthesis of the marine fungal natural product (-)-eurotiumin A using NotF in tandem with BvnB.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Integrative & Complementary Medicine
Cao Ning, Wang Chang-Hong
Summary: This article reviews the latest research on the biosynthesis of natural compounds TIAs and BCAs, focusing on the role of strictosidine synthase in this process and the sources and substrate specificity of related compounds derived from strictosidine. The presence of six-bladed four-stranded beta-propeller folds in many organisms other than plants may indicate similar functions among different organisms. The expression of the strictosidine synthase gene has a significant impact on the production of various compounds, which are mainly used in plant cell suspension culture for the production of valuable drugs and biosynthesis in other carriers.
CHINESE JOURNAL OF NATURAL MEDICINES
(2021)
Article
Chemistry, Multidisciplinary
Xiaoyu Liu, Kun He, Na Gao, Peiyun Jiang, Jun Lin, Yi Jin
Summary: A new radical-mediated, one-pot, multicomponent cascade reaction was developed for the synthesis of azide-biindole derivatives. Mechanistic studies showed the formation of nitrogen-centred free radicals which initiated the cascade reaction to obtain the final products. This methodology may have potential applications in constructing other azido heterocycles.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Matteo Faltracco, Said Ortega-Rosales, Elwin Janssen, Razvan C. Cioc, Christophe M. L. Vande Velde, Eelco Ruijter
Summary: The unexpected discovery in a seemingly trivial reaction led to the selective formation of a new carbazole product. This reaction, by carefully varying substituents, revealed a complex cascade mechanism with at least 10 elementary steps that could be directed towards different carbazole derivatives.
Article
Chemistry, Organic
Dharmendra Kumar, Dhananjay Chaudhary, Km Ishu, Suman Yadav, Naveen Kumar Maurya, Ruchir Kant, Malleswara Rao Kuram
Summary: A domino reaction sequence has been developed for the synthesis of pyrroloindolines, in which tryptamine derivatives and donor-acceptor diazo compounds are used as substrates. This reaction simultaneously forms three consecutive stereogenic centers, providing a convenient and efficient strategy for the construction of complex molecules. Copper catalysis enables the reaction to proceed smoothly at room temperature, and a wide range of substrates can be employed.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemical Research Methods
Joshua Misa, John M. Billingsley, Kanji Niwa, Rachel K. Yu, Yi Tang
Summary: This study reports the development of a yeast-based platform for high-titer production of the universal MIA precursor, strictosidine, enabling rapid access to downstream MIA natural products.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eryan Guo, Mengting Yuan, Lijun Xu, Qinjia Ren, Zihan Wang, Zixin Li, Zongyao Wu, Wenyuan Liu, Yucheng Zhao, Feng Feng, Jian Xu
Summary: The metabolomics and transcriptomics of Uncaria rhynchophylla were analyzed, and 31 alkaloids and 47,423 unigenes were identified. The relative contents of these alkaloids were evaluated and a proposed biosynthetic pathway for Tetracyclic oxindole alkaloids was devised. Three enzymes were identified as important catalytic enzymes for the synthesis of tryptamine, strictosidine, and 4,21-dehydrogeissochizine.
BIOORGANIC CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Minghui Fan, Liangbang Zou, Kaidi Tian, Guoqing Chen, Kai Cheng, Yong Li
Summary: This review provides a comprehensive coverage of stemmadenine alkaloids from early reports to July 2022, and briefly describes their diverse biological activities. Furthermore, the proposed biosynthetic pathway for stemmadenine and the conversion of stemmadenine-type alkaloids into vallesamine-type congeners are discussed in detail. Additionally, successful synthetic strategies to access the strained stemmadenine scaffolds are fully reviewed.
NATURAL PRODUCT REPORTS
(2023)
Article
Chemistry, Organic
Xiao-Yong Duan, Zhaohui Tian, Binghao Liu, Tao He, Liang-Liang Zhao, Mengdie Dong, Pengna Zhang, Jing Qi
Summary: This work describes the NHC-catalyzed Michael/Mannich/lactamization cascade reaction of enals with either indole-2-carboxaldehyde-derived aldimines or indole-7-carboxaldehyde-derived aldimines, allowing for the rapid assembly of optically active pyrroloindolones and pyrroloquinolinones derivatives under mild conditions with high yields, excellent enantioselectivities, and a broad substrate scope.
Article
Chemistry, Organic
An-Xiang Huang, Hu-Lin Zhu, Fan-Lin Zeng, Xiao-Lan Chen, Xian-Qiang Huang, Ling-Bo Qu, Bing Yu
Summary: 1-Acryloyl-2-cyanoindoles were discovered to be novel and efficient scaffolds in visible-light-induced persulfate-promoted cascade cyclization reactions. With this transition-metal-free photocatalytic procedure, various sulfonated/thiocyanated pyrrolo[1,2-a]indolediones were synthesized from 1-acryloyl-2-cyanoindoles with sulfonyl hydrazides/NH4SCN at room temperature under mild reaction conditions.
Article
Chemistry, Multidisciplinary
You-lu Pan, Xiao-meng Gong, Rong-rong Hao, Shen-xin Zeng, Zheng-rong Shen, Wen-hai Huang
Summary: A facile CuBr2 induced radical relay addition/cyclization reaction has been developed for the synthesis of a broad range of sulfonated compounds. Some of the synthesized compounds exhibited bioactivity against cancer cell lines. This protocol offers advantages of low-cost, base-free, simple operation, and broad functional group tolerance.
Article
Chemistry, Organic
Barbara Chatinovska, Rokas Gegevicius, Edvinas Orentas
Summary: This study obtains rapid access to both enantiomers of vellosimine and its derivatives from a readily affordable precursor. The strategy utilized desymmetrization via intramolecular cyclization to assemble a key intermediate with two differentiated carbonyl groups. The late-stage site selective indolization allows for a concise synthesis of vellosimines and a straightforward diversification of the alkaloid scaffold.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Jie Zhang, Lea G. Hansen, Olga Gudich, Konrad Viehrig, Laerke M. M. Lassen, Lars Schruebbers, Khem B. Adhikari, Paulina Rubaszka, Elena Carrasquer-Alvarez, Ling Chen, Vasil D'Ambrosio, Beata Lehka, Ahmad K. Haidar, Saranya Nallapareddy, Konstantina Giannakou, Marcos Laloux, Dushica Arsovska, Marcus A. K. Jorgensen, Leanne Jade G. Chan, Mette Kristensen, Hanne B. Christensen, Suresh Sudarsan, Emily A. Stander, Edward Baidoo, Christopher J. Petzold, Tune Wulff, Sarah E. O'Connor, Vincent Courdavault, Michael K. Jensen, Jay D. Keasling
Summary: This study demonstrates the de novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast, and in vitro chemical coupling to vinblastine. By integrating a very long biosynthetic pathway into yeast, the researchers have provided a scalable platform for producing over 3,000 natural MIAs and numerous new analogues.
Article
Biochemistry & Molecular Biology
Xiaozheng Wang, Dekun Kong, Tingting Huang, Fei Xu, Man-Cheng Tang, Zixin Deng, Shuangjun Lin
Summary: In this study, a new enzyme StnP2 was discovered to catalyze the biosynthesis of beta-Carboline alkaloids and exhibited catalytic activity towards various TH beta-C, highlighting the importance of flavoproteins.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Sarah Bierbaumer, Luca Schmermund, Alexander List, Christoph K. Winkler, Silvia M. Glueck, Wolfgang Kroutil
Summary: In this study, a concurrent biocatalytic reduction and photocatalytic oxidation process was demonstrated. By coupling the enantioselective biocatalytic sulfoxide reduction and light-dependent sulfoxidation, a cyclic deracemization process for nonracemic sulfoxides was achieved with excellent conversions and optical purity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Nico D. Fessner, Christopher Grimm, Matic Srdic, Hansjoerg Weber, Wolfgang Kroutil, Ulrich Schwaneberg, Anton Glieder
Summary: This study explores the synthetic potential of human P450 3A4 in diversifying natural product classes, resulting in the identification of 31 authentic human metabolites. With efficient expression levels in P. pastoris, this biocatalyst shows promising results for modifying natural products in a one-step fashion.
Article
Chemistry, Physical
Willem B. Breukelaar, Nakia Polidori, Amit Singh, Bastian Daniel, Silvia M. Guleck, Karl Gruber, Wolfgang Kroutil
Summary: The biocatalytic reduction of oxime moiety to amine group has recently been discovered, but the reaction pathway remained unclear. Through studying crystal structures, molecular dynamics simulations, and investigating biocatalytic cascades and intermediates, evidence suggests that the reaction proceeds via an imine intermediate rather than a hydroxylamine intermediate. The imine is further reduced by the ene-reductase to produce the amine product. A non-canonical tyrosine residue contributes to the catalytic activity by protonating the hydroxyl group of the oxime in the first reduction step.
Article
Chemistry, Applied
Philipp Petermeier, Christoph Kohlfuerst, Ana Torvisco, Roland C. C. Fischer, Alejandro Mata, Doris Dallinger, C. Oliver Kappe, Joerg H. H. Schrittwieser, Wolfgang Kroutil
Summary: Substituted piperidine rings are efficiently prepared with multiple stereocentres using multi-enzymatic and chemo-enzymatic methods from achiral diketoester precursors. Highly enantioselective transamination and diastereoselective reduction processes enable the synthesis of optically pure piperidines. This approach offers a more streamlined and efficient route for the synthesis of trisubstituted piperidines with potential applications in drug discovery.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Applied
P. Petermeier, C. Kohlfuerst, A. Torvisco, R. C. Fischer, A. Mata, D. Dallinger, C. O. Kappe, J. H. Schrittwieser, W. Kroutil
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Applied
Mathias Pickl, Markus Ebner, Samantha Gittings, Pere Clapes, Wolfgang Kroutil
Summary: Although optical pure amino alcohols are highly demanded, their synthesis remains challenging due to the requirement of elaborate protection strategies. This study presents a multi-enzymatic methodology that allows the synthesis of enantioenriched 1,3-amino alcohols from commodity chemicals. By utilizing a Type I aldolase and enzymatic transamination, both diastereomers of the 1,3-amino alcohol motif were accessible, resulting in the desired amino alcohols with high enantioselectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Sarah A. Berger, Christopher Grimm, Jonathan Nyenhuis, Stefan E. Payer, Isabel Oroz-Guinea, Joerg H. Schrittwieser, Wolfgang Kroutil
Summary: Mass spectrometry-based high-throughput screening methods combine the advantages of photometric or fluorometric assays and analytical chromatography. However, their limited use is due to the requirement of specialised and expensive hardware. We demonstrate that a common platform, single-quadrupole HPLC-MS, can be used for rapid analysis of diverse biotransformations by flow-injection mass spectrometry (FIA-MS), providing validated activity and selectivity information with a one-minute analytical run time per sample. Our results establish FIA-MS as a versatile and reliable alternative to traditional methods for screening enzymatic reactions.
Review
Chemistry, Physical
Veronique Alphand, Willem J. H. van Berkel, Valentina Jurkas, Selin Kara, Robert Kourist, Wolfgang Kroutil, Francesco Mascia, Marc M. Nowaczyk, Caroline E. Paul, Sandy Schmidt, Jelena Spasic, Paula Tamagnini, Christoph K. Winkler
Summary: The recent increase of interest in photocatalysis has expanded to biocatalysis and led to a surge in the development of light-dependent enzyme-mediated or enzyme-coupled processes. Reviewing the progress in photobiocatalysis, we suggest categorizing it into different disciplines and providing guidelines for reporting research results and performing photobiocatalytic reactions. Overall, we believe that this field enhances the diversity of biocatalytic reactions and harnesses the selectivity of enzymes in photocatalysis. We anticipate that the ongoing enthusiasm for light-dependent enzymatic processes will uncover new photobiocatalytic mechanisms, complementing biocatalysis with novel bond-forming reactions and innovative strategies for utilizing light as a sustainable energy source.
Article
Chemistry, Organic
Beata Zdun, Tamara Reiter, Wolfgang Kroutil, Pawel Borowiecki
Summary: We developed chemoenzymatic routes using low-cost starting materials and enzyme preparations to synthesize tenofovir. The key step involved stereoselective reduction or kinetic resolution using alcohol dehydrogenase or lipase as biocatalysts. By employing immobilized lipase in a mixture of vinyl acetate and toluene, the desired (R)-ester was obtained with high yield and optical purity. Alternatively, reduction of a ketone using lyophilized E. coli cells containing recombinant alcohol dehydrogenase resulted in excellent conversion and yield of the corresponding (R)-alcohol. The enzymatic strategy could be applied in the synthesis of tenofovir prodrug derivatives.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Correction
Chemistry, Physical
Stefan Simic, Migle Jakstaite, Wilhelm T. S. Huck, Christoph K. Winkler, Wolfgang Kroutil
Article
Chemistry, Multidisciplinary
Aleksandra Rudzka, Beata Zdun, Natalia Antos, Lia Martinez Montero, Tamara Reiter, Wolfgang Kroutil, Pawel Borowiecki
Summary: There is a need for biocatalysts capable of transferring hydrogen to prepare optically pure alcohols, especially for sterically demanding ketones. This study describes the biocatalytic potential of an anti-Prelog (R)-specific variant of Lactobacillus kefir ADH as a whole-cell biocatalyst for the reduction of prochiral carbonyl substrates. The results show that the biocatalyst exhibits activity towards a variety of ketones, producing optically active alcohol products with high conversion and excellent stereoselectivity.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Christopher Grimm, Simona Pompei, Kristina Egger, Michael Fuchs, Wolfgang Kroutil
Summary: Lignin-derived aryl methyl ethers have potential as carbon sources in chemistry. An alternative method for their demethylation is through cobalamin-dependent enzymes, which require a methyltransferase and a carrier protein. Fusion proteins, connecting the methyltransferase with the corrinoid-binding protein, showed better performance than separate proteins, enabling a simpler protocol for demethylation. The fusion enzyme has promising applications in diversifying natural products and valorizing lignin.
Article
Chemistry, Physical
Willem B. Breukelaar, Nakia Polidori, Amit Singh, Bastian Daniel, Silvia M. Glueck, Karl Gruber, Wolfgang Kroutil
Summary: The biocatalytic reduction of oxime to amine has been observed in ene-reductases transforming alpha-oximo beta-keto esters. Through structural analysis, molecular dynamics simulations, biocatalytic cascades, and investigation of possible intermediates, it has been determined that the reaction proceeds via an imine intermediate and not through a hydroxylamine intermediate. A non-canonical tyrosine residue in ene-reductase OPR3 was found to play a role in protonating the hydroxyl group of the oxime in the first reduction step.
Article
Chemistry, Multidisciplinary
Emmanuel Cigan, Jakob Pletz, Sarah A. Berger, Bettina Hierzberger, Michael Grilec-Zlamal, Alexander Steiner, Isabel Oroz-Guinea, Wolfgang Kroutil
Summary: This study demonstrates an efficient access to the morphinan scaffold using a combination of organic synthesis and enzymatic reactions. The synthesis of a medicinally important compound class, promorphinans, was achieved by minimizing protecting group techniques and utilizing biocatalysis.
Article
Chemistry, Physical
Pawel Borowiecki, Aleksandra Rudzka, Tamara Reiter, Wolfgang Kroutil
Summary: In this study, a sequential chemoenzymatic one-pot two-step deracemization protocol was developed for synthesizing enantiomeric Lisofylline. The protocol involved a tandem bi-enzymatic oxidation-reduction reaction sequence, which catalyzed the oxidation of Lisofylline to pentoxifylline using laccase and a redox mediator, and the subsequent reduction of pentoxifylline to generate enantiomeric Lisofylline using alcohol dehydrogenases. The method showcased high conversion rates and synthesis efficiency, providing both antipodes of Lisofylline in good yields and high enantiomeric excess.
CATALYSIS SCIENCE & TECHNOLOGY
(2022)