Article
Chemistry, Multidisciplinary
Xin Gao, Joshua R. Turek-Herman, Young Joo Choi, Ryan D. Cohen, Todd K. Hyster
Summary: This study demonstrates that engineered flavin-dependent 'ene'-reductases (EREDs) can catalyze radical additions into oximes with high stereoselectivity to prepare alpha-tertiary amines, which are common in pharmaceutical molecules. Two evolved EREDs were competent catalysts for this transformation, and mechanistic studies revealed the role of oximes in the enzyme templated charge-transfer complex. The products can be further derivatized for the synthesis of various motifs, showcasing the versatility of ERED photoenzymatic catalysis in organic synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Physical
Ewald P. J. Jongkind, Aurelie Fossey-Jouenne, Ombeline Mayol, Anne Zaparucha, Carine Vergne-Vaxelaire, Caroline E. Paul
Summary: Accessing chiral amines with high enantiomeric and diastereomeric excess was achieved through the development of a bi-enzymatic cascade using Old Yellow Enzyme family enzymes. Different unsaturated carbonyl substrates were successfully converted with up to 99% selectivity, showcasing the potential of this approach for diverse alkene substrates.
Article
Chemistry, Multidisciplinary
Soumitra V. Athavale, Shilong Gao, Zhen Liu, Sharath Chandra Mallojjala, Jennifer S. Hirschi, Frances H. Arnold
Summary: A biocatalytic intermolecular benzylic C-H amidation reaction has been developed, converting feedstock aromatic compounds to chiral amides with excellent enantioselectivity and high yields. The enzymatic reaction involves rate-determining nitrenoid formation followed by stepwise hydrogen atom transfer-mediated C-H functionalization.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Feng Cheng, Yi Chen, Shuai Qiu, Qiu-Yao Zhai, Hua-Tao Liu, Shu-Fang Li, Chun-Yue Weng, Ya-Jun Wang, Yu-Guo Zheng
Summary: Key residues regulating the stereopreference of a carbonyl reductase from Kluyveromyces marxianus (KmCR) were identified through semi-rational engineering, leading to the successful conversion of Prelog selectivity to complete anti-Prelog selectivity. This knowledge was then used to successfully predict and engineer the stereopreferences of other CRs sharing sequence identities with KmCR.
Article
Chemistry, Multidisciplinary
Karthik Sankaranarayanan, Klavs F. Jensen
Summary: Chemoenzymatic synthesis methods combine organic and enzyme chemistry to efficiently synthesize small molecules. A multistep retrosynthesis search algorithm is presented in this study to facilitate the chemoenzymatic synthesis of various compounds. The algorithm uses a synthesis planner and a biocatalytic reaction database to identify enzyme-catalyzed reactions and plan synthetic routes for pharmaceutical, specialty, and commodity chemicals. The approach successfully plans chemoenzymatic routes for different compounds and proposes alternative pathways as well.
Article
Chemistry, Multidisciplinary
Yingle Mao, Weijie Zhang, Zunyun Fu, Yanqiong Liu, Lin Chen, Xin Lian, Dan Zhuo, Jiewei Wu, Mingyue Zheng, Cangsong Liao
Summary: C(sp(3))-H oxyfunctionalization, the insertion of an O-atom into C(sp(3))-H bonds, is a challenging task in organic chemistry for site and stereoselectivity. Biocatalytic C(sp(3))-H oxyfunctionalization overcomes the limitations of small-molecule-mediated approaches by delivering catalyst-controlled selectivity. We have developed a subfamily of α-ketoglutarate-dependent iron dioxygenases that catalyze the site- and stereodivergent oxyfunctionalization of secondary and tertiary C(sp(3))-H bonds, providing concise synthetic routes towards four types of 92 α- and β-hydroxy acids with high efficiency and selectivity. This method offers a biocatalytic approach for the production of valuable chiral hydroxy acid building blocks.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Vladimir Kren, Wolfgang Kroutil, Melanie Hall
Summary: Kurt Faber, a synthetic organic chemist, has made significant contributions to the field of biocatalysis. His work has recognized the importance of natural catalysts in organic synthesis and has provided a solid foundation for this discipline. He has also been involved in teaching and mentoring young scientists, and his book "Biotransformations in Organic Chemistry" has become a renowned resource for chemists and biotechnologists. In recognition of his innovative contributions, he received the Biotrans senior award at the Biotrans 2021 symposium.
Article
Chemistry, Organic
Tobias Babl, Oliver Reiser
Summary: The first enantioselective synthesis of (S)-meptazinol in 14 steps from a commercially available compound and the formal synthesis of two anti-Alzheimer's agents are reported. A novel ring expansion reaction provides an effective entry to 3,3-disubstituted azepanes that represent the core for a variety of approved drugs.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Mohammad Faizan Bhat, Alejandro Prats Lujan, Mohammad Saifuddin, Gerrit J. Poelarends
Summary: In this study, we report a simple chemoenzymatic synthesis route for the preparation of chiral dihydrobenzoxazinones and dihydroquinoxalinones. These methods offer high selectivity and yield, and use readily available starting materials.
Article
Chemistry, Multidisciplinary
Markus Hobisch, Jelena Spasic, Lenny Malihan-Yap, Giovanni Davide Barone, Kathrin Castiglione, Paula Tamagnini, Selin Kara, Robert Kourist
Summary: This study demonstrates the use of internal illumination to overcome the cell density limitation of cyanobacterial biotransformations, achieving high reaction rates in a scalable photobioreactor.
Review
Chemistry, Multidisciplinary
Sergio Gonzalez-Granda, Lorena Escot, Ivan Lavandera, Vicente Gotor-Fernandez
Summary: The combination of metal and enzyme catalysis has attracted great attention in organic synthesis due to its ability to achieve diverse organic molecules with the stereospecificity displayed by enzymes. This minireview focuses on the action of metal species (Pd, Ru, Au, Ir, Fe, etc.) in combination with different enzymes, highlighting the design of sequential processes and concurrent cascades to overcome incompatibilities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Qi Chen, Bo-Bo Li, Lilan Zhang, Xin-Ru Chen, Xin-Xin Zhu, Fei-Fei Chen, Min Shi, Chun-Chi Chen, Yu Yang, Rey-Ting Guo, Weidong Liu, Jian-He Xu, Gao-Wei Zheng
Summary: An engineered IRED with significantly improved activity and stability was developed through three rounds of evolution. The use of this engineered enzyme allowed for complete reduction of a cyclic imine, resulting in high yield and high enantiomeric excess of an important chiral intermediate.
Article
Chemistry, Applied
Ram Subhawan Verma, Ranadeep Talukdar, Tazeen Azaz, Bhoopendra Tiwari
Summary: A direct catalytic method for the synthesis of chiral selenylated delta-lactones via [4+2] annulation has been achieved. The C5-selenylated dihydropyranones were obtained in high yield and with high enantioselectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Biochemistry & Molecular Biology
Katrina S. Madden, Peter M. T. Todd, Kouji Urata, Angela J. Russell, Kylie A. Vincent, Holly A. Reeve
Summary: Barriers to the adoption of biocatalysis in early stage medicinal chemistry are addressed using ketone reduction as a model reaction. Commercial alcohol dehydrogenase enzymes show wide substrate scope and high tolerance to chemical groups commonly used in drug discovery. A preliminary predictive pharmacophore-based screening tool is developed using substrate screening data, demonstrating the potential for developing such tools for commercially available enzymes without publicly available structures.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Kai Wu, Jinrong Yan, Xiaojing Wang, Xinai Yin, Guixiang Shi, Lei Yang, Fangling Li, Junhai Huang, Lei Shao
Summary: The study successfully enhanced the activity towards bulky diaryl ketones by engineering ADH seq5 to produce the mutant seq5-D150I. By optimizing reaction conditions, high enantiomeric excess of (S)-4-chlorophenylpyridylmethanol and (R)-4-chlorobenzhydrol were successfully synthesized with significantly increased yields.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Birgit Wiltschi, Tomislav Cernava, Alexander Dennig, Meritxell Galindo Casas, Martina Geier, Steffen Gruber, Marianne Haberbauer, Petra Heidinger, Enrique Herrero Acero, Regina Kratzer, Christiane Luley-Goedl, Christina A. Mueller, Julia Pitzer, Doris Ribitsch, Michael Sauer, Katharina Schmoelzer, Wolfgang Schnitzhofer, Christoph W. Sensen, Jung Soh, Kerstin Steiner, Christoph K. Winkler, Margit Winkler, Tamara Wriessnegger
BIOTECHNOLOGY ADVANCES
(2020)
Article
Chemistry, Physical
Luca Schmermund, Sarah Bierbaumer, Viktor K. Schein, Christoph K. Winkler, Selin Kara, Wolfgang Kroutil
Article
Chemistry, Physical
Etta Jost, Masoud Kazemi, Valerija Mrkonjic, Fahmi Himo, Christoph K. Winkler, Wolfgang Kroutil
Article
Chemistry, Multidisciplinary
Christoph K. Winkler, Joerg H. Schrittwieser, Wolfgang Kroutil
Summary: Biocatalysis, using defined enzymes for organic transformations, has become a common tool in organic synthesis and industry. The high activity and selectivity observed in biotransformations are achieved through precise control of the active site and catalyst. Enzyme engineering allows adaptation of catalysts to different reactions, providing opportunities for novel transformations and increasing efficiency.
ACS CENTRAL SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Luca Schmermund, Susanne Reischauer, Sarah Bierbaumer, Christoph K. Winkler, Alba Diaz-Rodriguez, Lee J. Edwards, Selin Kara, Tamara Mielke, Jared Cartwright, Gideon Grogan, Bartholomaus Pieber, Wolfgang Kroutil
Summary: The redox potential of a carbon nitride photocatalyst can be tuned by changing the irradiation wavelength, enabling selective generation of enantiomers of phenylethanol through photo-chemo-enzymatic cascades. Green light irradiation leads to (R)-1-phenylethanol, while blue light irradiation results in (S)-1-phenylethanol.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Christoph K. Winkler, Stefan Simic, Valentina Jurkas, Sarah Bierbaumer, Luca Schmermund, Silvan Poschenrieder, Sarah A. Berger, Elisa Kulterer, Robert Kourist, Wolfgang Kroutil
Summary: Photobiocatalysis is an emerging synthesis approach that is gaining attention, with only a few commercially available reactor systems due to its youth. A newly developed photoreactor allows parallel parameter screening for optimization, demonstrated in applications such as light-dependent decarboxylation and photosynthetic oxygen production.
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
Isabel Oroz-Guinea, Christoph K. Winkler, Silvia M. Glueck, Klaus Ditrich, Melanie Weingarten, Michael Breuer, Doreen Schachtschabel, Wolfgang Kroutil
Summary: The study demonstrates a regio- and stereoselective mono-reduction method for pseudoionone using OYE1 from Saccharornyces postorianus, achieving excellent conversion at high substrate concentrations. Furthermore, utilizing E. coli cells containing overexpressed enzyme instead of purified enzyme allows for efficient conversion without the need for organic cosolvent. In addition, the ene-reductase from Zyrnornonas mobilis enables stereoselective reduction of the (E,Z)-pseudoion-one isomer, providing both (E)-geranylacetone and (E,Z)-pseudoionone with high isomeric excess.
Review
Chemistry, Multidisciplinary
Stefan Simic, Erna Zukic, Luca Schmermund, Kurt Faber, Christoph K. Winkler, Wolfgang Kroutil
Summary: Biocatalysis, using enzymes for organic synthesis, is a powerful tool for the synthesis of active pharmaceutical ingredients (APIs). Developments in molecular biology methods have led to the rapid development of process-stable enzymes through directed evolution. Enzymes are widely employed in the synthesis of small molecule APIs, enabling more efficient and sustainable routes.
Article
Chemistry, Multidisciplinary
Valentina Jurkas, Florian Weissensteiner, Piera De Santis, Stephan Vrabl, Frieda A. Sorgenfrei, Sarah Bierbaumer, Selin Kara, Robert Kourist, Pramod P. Wangikar, Christoph K. Winkler, Wolfgang Kroutil
Summary: A transmembrane electron shuttling system propelled by cyanobacterial photosynthesis was established to drive extracellular NAD(P)H-dependent redox reactions, achieving high conversions and optical purity of products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Stefan Simic, Migle Jakstaite, Wilhelm T. . S. Huck, Christoph K. Winkler, Wolfgang Kroutil
Summary: The challenges of light-dependent biocatalytic transformations of lipophilic substrates in aqueous media are addressed through continuous flow reactions. The immobilization of the catalyst on a carrier or using a homogeneous system is determined by the photostability of the catalyst. Homogeneous conditions in the CvFAP-catalyzed photodecarboxylation of palmitic acid achieved a high space-time yield, demonstrating the advantage of continuous flow for photobiocatalytic processes.
Review
Chemistry, Multidisciplinary
Sarah Bierbaumer, Maren Nattermann, Luca Schulz, Reinhard Zschoche, Tobias J. Erb, Christoph K. Winkler, Matthias Tinzl, Silvia M. Glueck
Summary: Enzymatic carbon dioxide fixation is important for converting inorganic carbon from the atmosphere into organic biomass. However, the thermodynamics and utilization of CO2 make it challenging for biotechnological applications. This review provides an overview of natural CO2-fixing enzymes, discusses their applications, and suggests strategies for improving efficiency. It also explores the potential of using reduced CO2 derivates and offers a techno-economic perspective on reducing CO2 emissions.
Article
Chemistry, Physical
Bastian Daniel, Chiam Hashem, Marlene Leithold, Theo Sagmeister, Adrian Tripp, Holly Stolterfoht-Stock, Julia Messenlehner, Ronan Keegan, Christoph K. Winkler, Jonathan Guyang Ling, Sabry H. H. Younes, Gustav Oberdorfer, Farah Diba Abu Bakar, Karl Gruber, Tea Pavkov-Keller, Margit Winkler
Summary: The study focuses on the structural and functional information of the reductase domain of CAR from Neurospora crassa, providing insights into aldehyde production and overreduction mechanisms.
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.
Correction
Chemistry, Physical
Stefan Simic, Migle Jakstaite, Wilhelm T. S. Huck, Christoph K. Winkler, Wolfgang Kroutil
