| Mutational biosynthesis of ansamitocin antibiotics: a diversity-oriented approach to exploit biosynthetic flexibility. | |
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MedLine Citation:
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PMID: 22238146 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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New ansamitocin derivatives were prepared by feeding aminobenzoic acid derivatives to cultures of Actinosynnema pretiosum HGF073, a mutant strain blocked in the biosynthesis of the required 3-amino-5-hydroxybenzoic acid (AHBA) starter unit. Use of several aminobenzoic acids as precursors led to a spectrum of products, reflecting the sequence of post-PKS tailoring steps involved in the generation of ansamitocins and adding novel aspects to the published suggestion model of post-PKS tailoring logic and flexibility. The studies provide insights into the substrate flexibility of the enzymes required for ansamitocin biosynthesis in A. pretiosum, whereas preliminary biological testing of the derivatives isolated and fully characterized by NMR spectroscopy allowed structure-activity relationship assignments to be made for a variety of intermediates occurring during the post-PKS tailoring sequence in ansamitocin biosynthesis. |
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Authors:
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Tobias Knobloch; Kirsten Harmrolfs; Florian Taft; Binia Thomaszewski; Florenz Sasse; Andreas Kirschning |
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Publication Detail:
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Type: Journal Article Date: 2011-01-27 |
Journal Detail:
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Title: Chembiochem : a European journal of chemical biology Volume: 12 ISSN: 1439-7633 ISO Abbreviation: Chembiochem Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2012-01-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100937360 Medline TA: Chembiochem Country: Germany |
Other Details:
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Languages: eng Pagination: 540-7 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Zentrum für Biomolekulare Wirkstoffe (BMWZ), Leibniz Universität, Hannover Schneiderberg 1B, 30167 Hannover (Germany), Fax: (+49) 511-762-3011. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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