C1 Refereed scientific book
Biosynthetic anthracycline variants
Authors: Niemi J, Metsa-Ketela M, Schneider G, Mantsala P
Publication year: 2008
Journal:: Topics in Current Chemistry
Journal name in source: ANTHRACYCLINE CHEMISTRY AND BIOLOGY I: BIOLOGICAL OCCURENCE AND BIOSYNTHESIS, SYNTHESIS AND CHEMISTRY
Journal acronym: TOP CURR CHEM
Volume: 282
First page : 75
Last page: 99
Number of pages: 25
ISBN: 978-3-540-75814-3
ISSN: 0340-1022
DOI: https://doi.org/10.1007/128_2007_13
Abstract
In addition to synthetic and semisynthetic methods, new anthracycline structures have been generated by biosynthetic methods: genetic engineering of Streptomyces production strains, bioconversion and chemoenzymatic synthesis. In this review, we discuss the set of molecules potentially producible by biosynthetic methods and which structures have so far been realized. Biosynthetic variation in the anthracycline molecule manifests itself either as structure changes in the tetracyclic aglycone, or as variation in glycosylation. Understanding the biosynthetic sequence and knowledge of the substrate specificities of the enzymes participating in it enable rational generation of new anthracycline diversity. Future possibilities include protein engineering of the biosynthetic enzymes to improve the production of new structural combinations.
In addition to synthetic and semisynthetic methods, new anthracycline structures have been generated by biosynthetic methods: genetic engineering of Streptomyces production strains, bioconversion and chemoenzymatic synthesis. In this review, we discuss the set of molecules potentially producible by biosynthetic methods and which structures have so far been realized. Biosynthetic variation in the anthracycline molecule manifests itself either as structure changes in the tetracyclic aglycone, or as variation in glycosylation. Understanding the biosynthetic sequence and knowledge of the substrate specificities of the enzymes participating in it enable rational generation of new anthracycline diversity. Future possibilities include protein engineering of the biosynthetic enzymes to improve the production of new structural combinations.
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