Special Issue "Asymmetric and Selective Biocatalysis"
A special issue of Catalysts (ISSN 2073-4344).
Deadline for manuscript submissions: closed (31 October 2016)
Prof. Jose M. Palomo
Prof. Dr. Cesar Mateo
The preparation of pure chiral building blocks with the desired configuration is extremely important in different areas, especially in the production of pharmaceuticals. In this way, biocatalysts (cells, enzymes, catalytic antibodies, or ribozymes) represent the best alternative to the chemical processes because of the high regio- and enantio-selectivity towards different substrates at very mild conditions.
This Special Issue will be focused on innovative and novel research in “Asymmetric and Selective Biotransformations”.
Prof. Dr. Jose M. Palomo
Prof. Dr. Cesar Mateo
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Catalysts is an international peer-reviewed open access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
- kinetic resolutions of racemic mixtures
- asymmetric synthesis
- C-C bonding formation
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: Tandem Reactions Combining Biocatalysts and Chemical Catalysts for Asymmetric Synthesis
Authors: Yajie Wang and Huimin Zhao,
Affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign.
Abstract: The application of biocatalysts in the synthesis of fine chemicals and medicinal compounds has grown significantly in recent years. Particularly, the development of either sequential or one-pot tandem catalytic system combining the reactivity of a chemical catalyst with the selectivity engendered by the active site of a protein has proved to be appealing since it can achieve levels of chemo-, regio-, and stereo- selectivity that are unattainable with a small molecule catalyst. Engineered or artificial metalloenzymes also widen the range of reactivities and catalyzed reactions that are potentially employable. This review presents some of the most recent (2013-2016) examples that combined transition metal catalysis with enzymatic catalysis.
Title: Evaluation of Sucrose Synthase and O-Glycosyltransferase Fusion Proteins
Authors: Griet Dewitte1,°, Margo Diricks1,°, Ophelia Gevaert1, Oliver Spadiut2 and Tom Desmet1,*
Affiliations: 1Ghent University, Centre for Industrial Biotechnology and Biocatalysis, Department of Biochemical and Microbial Technology, Coupure Links 653, B-9000 Ghent, Belgium
2 Vienna University of Technology, Institute of Chemical Engineering, Research Area Biochemical Engineering, Gumpendorfer Strasse 1a, A-1060 Vienna, Austria
°These authors contributed equally to this work
*Correspondence: firstname.lastname@example.org; Tel.: +32-9-264-9920
Abstract: Glucosyltransferases are effective biocatalysts for the glucosylation of small compounds such as polyphenols. However, their preparative application requires efficient methods to generate expensive UDP-sugar donors. Interestingly, sucrose synthases catalyse the conversion of cheap sucrose into UDP-sugars. Here, we describe the in-frame fusion between a mutant sucrose synthase from Acidithiobacillus caldus (SuSy) and a promiscuous glycosyltransferase from Stevia rebaudiana (UGT). Variation of linker and order of this bacterial-plant fusion protein yielded three bifunctional enzymes exhibiting increased enzymatic activities when compared to native UGT and SuSy. In this way, the cost-efficient and selective glucosylation of the anti-oxidant catechin was enabled.
Keywords: biocatalyst; glycosylation; fusion; protein
Title: Old Yellow Enzyme-catalysed asymmetric hydrogenation with cofactor analogues: a journey to find family roots
Authors: Caroline Paul and Dirk Tischler
Abstract: Asymmetric hydrogenation of activated alkenes by Old Yellow Enzymes (OYEs) has a significant interest in industrial processes. The dependency of OYEs on the nicotinamide coenzyme can now be circumvented by established recycling systems, or even better, with the recently reported nicotinamide coenzyme biomimetics (NCBs). Certain OYEs were found to exhibit higher catalytic activity with several NCB analogues. In this review we classify OYE families according to various parameters and relate their activity data with the current NCBs.
Title: Hydrolysis vs. Aminolysis: Directed Optimization of Both Activities via Phage Display and Covalent Acyl-Enzyme Selection
Authors: Sabrina Gissel1, Sandra Liebscher1, Li Yuan2, Sven Pfeifer2, Christoph Meyer1,3, Lars Franke1, Bianka Hartrodt1, and Frank Bordusa1*
Affiliations:1Institute of Biochemistry/Biotechnology, Martin-Luther-University Halle/Wittenberg, Kurt-Mothes-Straße 3, D-06120 Halle/Saale (Germany)
2 Junior research group – artificial binding proteins, Heinrich-Damerow-Straße 4, D-06120 Halle/Saale (Germany)
3 Eucodis Bioscience GmbH Deutschland, Heinrich-Damerow-Straße 4, D-06120 Halle/Saale (Germany)
Abstract: This study establishes the Phage Display technology as suitable in vitro selection system for directed optimization of the previously designed trypsiligase used for the site-specific synthesis of antibody drug conjugates. In contrast to the conventional application of this evolutionary technology to improve typically the specificity or binding behavior of enzymes or proteins, focus was exclusively laid on the systematic reduction of the biocatalyst’s native secondary hydrolysis activity impairing the synthetic properties of the designed enzyme. For this purpose, an original selection approach based on the catalytic mechanism of trypsiligase was established using the covalent acyl-enzyme intermediate as novel pivot for the selection process. The general function of the approach was successfully validated in a first experimental trial entailing the identification of trypsiligase variants with specifically improved catalytic properties. The results led further assume that besides trypsiligase also the targeted engineering of other enzymes, which likewise generate acyl-enzyme intermediates during catalysis, should profit from the designed optimization approach.
Keywords: Phage Display, Evolution, Enzyme Engineering, Antibody-Drug-Conjugates, Hydrolases
Title: Regioselective chemoenzymatic syntheses of chromogenic substrates for feruloyl esterases
Authors: Olga Gherbovet 1, Fernando Ferreira 1, Mélanie Ragon 1, Julien Durand 1, Sophie Bozonnet 1, Michael J. O’Donohue 1 and Régis Fauré 1,*
Affiliation:1LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France
*Correspondence: email@example.com; Tel.: +33-561-55-9488
Abstract: Although feruloyl esterases constitute an important sub-group of hydrolytic enzymes involved in the deconstruction of plant cell wall polysaccharides, their identification and detailed characterization are still challenging topics because of the availability of ad hoc substrates. In this respect, devoted chromogenic substrates are valuable tools to provide quick and easy detection of enzyme-mediated hydrolysis of the ester bond, which can be readily monitored through color change. Both new and commercially available ferulate derivatives were prepared by regioselective chemoenzymatic synthetic routes and their efficiency as substrates for type A feruloyl esterase from Aspergillus niger was evaluated. The synthetic pathways leading to indolyl, (chloro)nitrophenyl and 4-nitrocatechol O-5 feruloylated-α-L-arabinofuranosides were significantly shortened, and therefore corresponding overall yields enhanced, by using enzymatic transesterification of ferulic acid from its active vinyl ester form to the primary hydroxyl group of the α-L-arabinofuranosyl units with Lipolase 100T (from Thermomyces lanuginosus). Furthermore, feruloylated-butanetriol 4-nitrocatechol analog containing a cleavable linker arm instead of a carbohydrate moiety was also obtained in 12% overall yield in 4 steps, combining regioselective functionalization of 4NTC and enzymatic transesterification. The practical synthesis at preparative scale of this library of chromogenic probes makes easier further investigation of feruloyl esterases.
Keywords: biocatalysis; transesterification; screening; CAZymes; ferulic ester hydrolysis
Title: Efficient production of enantiopure D-lysine from L-lysine by lysine racemase and decarboxylase coupled system
Authors: Xin Wang, Li Yang, Weijia Cao, Hanxiao Ying, Kequan Chen*, Pingkai Ouyan
Affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, Jiangsu, China
Title: A General Strategy For Stereoselective Chemoenzymatic Synthesis Of Optically Active Aryl-Substituted Oxygen Heterocycles
Authors: Paola Vitale,* Antonia Digeo, Filippo Maria Perna, Gennaro Agrimi, Antonio Scilimati, Antonio Salomone, Cosimo Cardellicchio, and Vito Capriati*
Abstract:We introduce a new and extremely efficient, general strategy for highly stereoselective chemoenzymatic synthesis of optically active α-aryl-substituted oxygen heterocycles. This is based on the biocatalytic asymmetric reduction of halogeno-aryl ketones run in the presence of whole cell biocatalysts,and followed by a stereospecific cyclization of the corresponding halohydrins into the target heterocycles. Some bench bioreduction processes catalyzed by different whole cells microorganisms (bakers' yeast, Kluyveromyces marxianus CBS 6556 and Saccharomyces cerevisiae CBS 7336, Lactobacillus reuteri DSM 20016) have been preliminarily screened in order to optimize the experimental conditions and to choose the more suitable biocatalyst. Among the tested biocatalysts, bakers' yeast was found to provide the best yields and the highest enantiomeric ratios (ers) in the bioreductions of α-, β-, and γ-chloro-aryl ketones. In the presence of tBuOK, the obtained optically active chlorohydrins could be quantitatively cyclized into the corresponding α-aryl-substituted cyclic ethers without erosion of the enantiomeric excess. In this way, valuable, chiral non-racemic functionalized oxygen heterocycles [e.g., (S)-styrene oxide, 98% yield, 91:9er; (S)-2- phenyloxetane, 98% yield, 99:1 er; (S)-2-phenyltetrahydrofuran, 98% yield, 93:7 er], amenable to be further elaborated, can be generated from prochiral precursors. Since the wild-type whole-cell biocatalyst selected (baker’s yeast) is cheap and commercially available, the discussed methodology is considered auspicious for setting up industrially relevant and cost-effective biotransformations for a large-scale production of oxygen heterocycles.
Title: Mechanistic and structural insight to an evolved benzoylformate decarboxylase with enhanced pyruvate decarboxylase activity
Authors: Michael J. McLeish, et al.
Affiliations: Department of Chemistry & Chemical Biology, Indiana University-Purdue University Indianapolis (IUPUI), 402 N. Blackford St. LD 326D, Indianapolis IN 46202
Abstract: Benzoylformate decarboxylase (BFDC) and pyruvate decarboxylase (PDC) are thiamin diphosphate-dependent enzymes that share some structural and mechanistic similarities. Both enzymes catalyze the nonoxidative decarboxylation of 2-keto acids, yet differ considerably in their substrate specificity. In particular, the BFDC from P. putida exhibits very limited activity with pyruvate, whereas the PDCs from S. cerevisiae or from Z. mobilis show virtually no activity with benzoylformate (phenylglyoxylate). Previously, saturation mutagenesis was used to generate the BFDC T377L/A460Y variant. This variant exhibited a greater than 10,000-fold increase in pyruvate/benzoylformate substrate utilization ratio compared to that of wtBFDC. Much of this change could be attributed to an improvement in the Km value for pyruvate and, concomitantly, a decrease in the kcat value for benzoylformate. However, the steady-state data did not provide any details about changes in individual catalytic steps. To gain insight into the changes in conversion rates of pyruvate and benzoylformate to acetaldehyde and benzaldehyde, respectively, by the BFDC T377L/A460Y variant, reaction intermediates of both substrates were analyzed by NMR and microscopic rate constants for the elementary catalytic steps were calculated. Herein we also report the high resolution X-ray structure of the BFDC T377L/A460Y variant, which helps to address the structural basis for the observed changes in substrate specificity.