C1 Vertaisarvioitu tieteellinen erillisteos
Biosynthetic anthracycline variants
Tekijät: Niemi J, Metsa-Ketela M, Schneider G, Mantsala P
Julkaisuvuosi: 2008
Lehti:: Topics in Current Chemistry
Tietokannassa oleva lehden nimi: ANTHRACYCLINE CHEMISTRY AND BIOLOGY I: BIOLOGICAL OCCURENCE AND BIOSYNTHESIS, SYNTHESIS AND CHEMISTRY
Lehden akronyymi: TOP CURR CHEM
Vuosikerta: 282
Aloitussivu: 75
Lopetussivu: 99
Sivujen määrä: 25
ISBN: 978-3-540-75814-3
ISSN: 0340-1022
DOI: https://doi.org/10.1007/128_2007_13
Tiivistelmä
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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