Biosynthetic anthracycline variants

: Niemi J, Metsa-Ketela M, Schneider G, Mantsala P

: 2008

: Topics in Current Chemistry

: ANTHRACYCLINE CHEMISTRY AND BIOLOGY I: BIOLOGICAL OCCURENCE AND BIOSYNTHESIS, SYNTHESIS AND CHEMISTRY

: TOP CURR CHEM

: 282

: 75

: 99

: 25

: 978-3-540-75814-3

: 0340-1022

DOI: https://doi.org/10.1007/128_2007_13

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.