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Biotechnological application of steroidogenic cytochromes P450
Full text linkSynthetic glucocorticoids are of high pharmaceutical value due to their anti-inflammatory and immunosuppressive effects. The low-yield chemical synthesis of glucocorticoids consists of multiple steps and includes toxic compounds as well as unwished by-product formation. Thus, one intends to replace this process by a more sustainable biocatalytic alternative.
The work presented here demonstrates an enzyme-mediated approach to produce the synthetic glucocorticoid premedrol, a precursor of methylprednisolone (medrol), by a one-step hydroxylation at carbon atom 21catalyzed by bovine CYP21A2, which belongs to the protein superfamily of cytochromes P450. Therefore, a CYP21A2-based whole-cell system was established, by which a maximum yield of 0.65 g/L premedrol could be achieved - a promising perspective for an industrial application.
With regard to a molecular evolution of CYP21A2 as well as an elucidation of the biocatalytic ability of orphan CYPs in a high-throughput microtiter scale, the indole-deficient Escherichia coli strain C43(DE3)_∆tnaA was generated, since indole is an inhibitor of some CYPs and massively impedes a screening. Applying C43(DE3)_∆tnaA in biotransformation resulted in a significantly higher product formation in case of CYP21A2 as well as of CYP264A1 from the myxobacterium Sorangium cellulosum So ce56 and thus, serves as convenient host in future screening procedures.Synthetische Glucocorticoide sind aufgrund ihrer antiinflammatorischen und immunsuppressiven Wirkung von hohem pharmazeutischem Wert. Die chemische Synthese von Glucocorticoiden besteht aus mehreren Schritten und beinhaltet die Verwendung toxischer Substanzen als auch die Bildung unerwünschter Nebenprodukte. Daher soll dieser Prozess durch ein nachhaltigeres biokatalytisches Verfahren ersetzt werden.
Die vorliegende Arbeit demonstriert eine biokatalytische Herangehensweise zur Produktion des synthetischen Glucocorticoids Premedrol, einem Vorläufer von Methylprednisolon (Medrol), durch eine einstufige Hydroxylierung am C21, welche durch das zur Proteinsuperfamilie der Cytochrome P450 gehörende steroidogene bovine CYP21A2 katalysiert wird. Daher wurde ein CYP21A2-basiertes Ganzzellsystem etabliert, mit Hilfe dessen eine maximale Premedrolausbeute von 0,65 g/l erzielt werden konnte – eine vielversprechende Perspektive im Hinblick auf eine industrielle Anwendung.
Hinsichtlich einer molekularen Evolution von CYP21A2 und einer Aufklärung des biokatalytischen Potentials unbekannter CYPs durch ein Hochdurchsatz-Screening wurde der Indol defiziente Escherichia coli Stamm C43(DE3)_∆tnaA generiert, da Indol einige CYPs inhibiert und somit ein Screening erschwert. Ein Umsatz mit C43(DE3)_∆tnaA resultierte in einer signifikant höheren Produktbildung im Falle des CYP21A2 und des CYP264A1 aus Sorangium cellulosum So ce56 und ist somit ein geeigneter Wirtsorganismus für künftige Screeningverfahren
Biotechnologische Anwendung steroidogener Cytochrome P450
Full text linkSynthetic glucocorticoids are of high pharmaceutical value due to their anti-inflammatory and immunosuppressive effects. The low-yield chemical synthesis of glucocorticoids consists of multiple steps and includes toxic compounds as well as unwished by-product formation. Thus, one intends to replace this process by a more sustainable biocatalytic alternative.
The work presented here demonstrates an enzyme-mediated approach to produce the synthetic glucocorticoid premedrol, a precursor of methylprednisolone (medrol), by a one-step hydroxylation at carbon atom 21catalyzed by bovine CYP21A2, which belongs to the protein superfamily of cytochromes P450. Therefore, a CYP21A2-based whole-cell system was established, by which a maximum yield of 0.65 g/L premedrol could be achieved - a promising perspective for an industrial application.
With regard to a molecular evolution of CYP21A2 as well as an elucidation of the biocatalytic ability of orphan CYPs in a high-throughput microtiter scale, the indole-deficient Escherichia coli strain C43(DE3)_∆tnaA was generated, since indole is an inhibitor of some CYPs and massively impedes a screening. Applying C43(DE3)_∆tnaA in biotransformation resulted in a significantly higher product formation in case of CYP21A2 as well as of CYP264A1 from the myxobacterium Sorangium cellulosum So ce56 and thus, serves as convenient host in future screening procedures.Synthetische Glucocorticoide sind aufgrund ihrer antiinflammatorischen und immunsuppressiven Wirkung von hohem pharmazeutischem Wert. Die chemische Synthese von Glucocorticoiden besteht aus mehreren Schritten und beinhaltet die Verwendung toxischer Substanzen als auch die Bildung unerwünschter Nebenprodukte. Daher soll dieser Prozess durch ein nachhaltigeres biokatalytisches Verfahren ersetzt werden.
Die vorliegende Arbeit demonstriert eine biokatalytische Herangehensweise zur Produktion des synthetischen Glucocorticoids Premedrol, einem Vorläufer von Methylprednisolon (Medrol), durch eine einstufige Hydroxylierung am C21, welche durch das zur Proteinsuperfamilie der Cytochrome P450 gehörende steroidogene bovine CYP21A2 katalysiert wird. Daher wurde ein CYP21A2-basiertes Ganzzellsystem etabliert, mit Hilfe dessen eine maximale Premedrolausbeute von 0,65 g/l erzielt werden konnte – eine vielversprechende Perspektive im Hinblick auf eine industrielle Anwendung.
Hinsichtlich einer molekularen Evolution von CYP21A2 und einer Aufklärung des biokatalytischen Potentials unbekannter CYPs durch ein Hochdurchsatz-Screening wurde der Indol defiziente Escherichia coli Stamm C43(DE3)_∆tnaA generiert, da Indol einige CYPs inhibiert und somit ein Screening erschwert. Ein Umsatz mit C43(DE3)_∆tnaA resultierte in einer signifikant höheren Produktbildung im Falle des CYP21A2 und des CYP264A1 aus Sorangium cellulosum So ce56 und ist somit ein geeigneter Wirtsorganismus für künftige Screeningverfahren
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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