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      Draft Genome Sequences of Three Actinobacteria Strains Presenting New Candidate Organisms with High Potentials for Specific P450 Cytochromes

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          ABSTRACT

          The three Actinobacteria strains Streptomyces platensis DSM 40041 , Pseudonocardia autotrophica DSM 535, and Streptomyces fradiae DSM 40063 were described to selectively oxyfunctionalize several drugs. Here, we present their draft genomes to unravel their gene sets encoding promising cytochrome P450 monooxygenases associated with the generation of drug metabolites.

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          Cytochrome P450 monooxygenases: an update on perspectives for synthetic application.

          Cytochrome P450 monooxygenases (P450s) are versatile biocatalysts that catalyze the regio- and stereospecific oxidation of non-activated hydrocarbons under mild conditions, which is a challenging task for chemical catalysts. Over the past decade impressive advances have been achieved via protein engineering with regard to activity, stability and specificity of P450s. In addition, a large pool of newly annotated P450s has attracted much attention as a source for novel biocatalysts for oxidation. In this review we give a short up-to-date overview of recent results on P450 engineering for technical applications including aspects of whole-cell biocatalysis with engineered recombinant enzymes. Furthermore, we focus on recently identified P450s with novel biotechnologically relevant properties. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Recombinant human cytochrome P450 monooxygenases for drug metabolite synthesis.

            Cytochrome P450 monooxygenases (CYPs) are important enzymes in the metabolism of xenobiotics. Therefore, several approaches to clone and overexpress the human isoforms have been made. In addition to microsomes or S9 preparations, these recombinant human isoforms have found diverse application in drug development. We discuss and give examples of the use of bacterial whole cell systems with rec. human CYPs for the preparative scale synthesis of drug metabolites.
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              Genome mining approach for the discovery of novel cytochrome P450 biocatalysts.

              Cytochrome P450 enzymes (P450s) are able to regioselectively and stereoselectively introduce oxygen into organic compounds under mild reaction conditions. These monooxygenases in particular easily catalyze the insertion of oxygen into less reactive carbon-hydrogen bonds. Hence, P450s are of considerable interest as oxidation biocatalysts. To date, although several P450s have been discovered through screening of microorganisms and have been further genetically engineered, the substrate range of these biocatalysts is still limited to fulfill the requirements for a large number of oxidation processes. On the other hand, the recent rapid expansion in the number of reported microbial genome sequences has revealed the presence of an unexpectedly vast number of P450 genes. This large pool of naturally evolved P450s has attracted much attention as a resource for new oxidation biocatalysts. In this review, we focus on aspects of the genome mining approach that are relevant for the discovery of novel P450 biocatalysts. This approach opens up possibilities for exploitation of the catalytic potential of P450s for the preparation of a large choice of oxidation biocatalysts with a variety of substrate specificities.
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                Author and article information

                Journal
                Genome Announc
                Genome Announc
                ga
                ga
                GA
                Genome Announcements
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2169-8287
                13 July 2017
                July 2017
                : 5
                : 28
                : e00532-17
                Affiliations
                [a ]Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany
                [b ]Novartis Pharma AG, Novartis Institutes of Biomedical Research, Basel, Switzerland
                [c ]c-LEcta GmbH, Leipzig, Germany
                [d ]Heinrich Heine University, Institute of Biochemistry, Düsseldorf, Germany
                [e ]Kappa Bioscience, Oslo, Norway
                Author notes
                Address correspondence to Christian Grumaz, christian.grumaz@ 123456igb.fraunhofer , or Kai Sohn, kai.sohn@ 123456igb.fraunhofer.de .
                [*]

                Present address: Stephan Luetz, TU Dortmund University, Department of Biochemical and Chemical Engineering, Dortmund, Germany.

                Article
                genomeA00532-17
                10.1128/genomeA.00532-17
                5511904
                28705965
                7cc3b040-8bcc-4467-a4f8-196c3c6b82cc
                Copyright © 2017 Grumaz et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 1 May 2017
                : 15 May 2017
                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 7, Pages: 2, Words: 1051
                Funding
                Funded by: Bundesministerium für Bildung und Forschung (BMBF) https://doi.org/10.13039/501100002347
                Award ID: 031A223B
                Award Recipient : Christian Grumaz Award Recipient : Yevhen Vainshtein Award Recipient : Philipp Kirstahler Award Recipient : Kai Sohn
                Funded by: Bundesministerium für Bildung und Forschung (BMBF) https://doi.org/10.13039/501100002347
                Award ID: 031A223A
                Award Recipient : Thomas Hilberath Award Recipient : Anne Worsch Award Recipient : Marco Girhard Award Recipient : Vlada B. Urlacher
                Categories
                Prokaryotes
                Custom metadata
                July 2017

                Genetics
                Genetics

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