Refereed review article in scientific journal (A2)
Anthracyclines: biosynthesis, engineering and clinical applications
List of Authors: Hulst Mandy B., Grocholski Thadee, Neefjes Jacques J.C., van Wezel Gilles P., Metsä-Ketelä Mikko
Publisher: Royal Society of Chemistry
Publication year: 2022
Journal: Natural Product Reports
Journal name in source: NATURAL PRODUCT REPORTS
Journal acronym: NAT PROD REP
Volume number: 39
Issue number: 4
Start page: 814
End page: 841
Number of pages: 28
ISSN: 0265-0568
eISSN: 1460-4752
DOI: http://dx.doi.org/10.1039/d1np00059d
Abstract
Covering: January 1995 to June 2021 Anthracyclines are glycosylated microbial natural products that harbour potent antiproliferative activities. Doxorubicin has been widely used as an anticancer agent in the clinic for several decades, but its use is restricted due to severe side-effects such as cardiotoxicity. Recent studies into the mode-of-action of anthracyclines have revealed that effective cardiotoxicity-free anthracyclines can be generated by focusing on histone eviction activity, instead of canonical topoisomerase II poisoning leading to double strand breaks in DNA. These developments have coincided with an increased understanding of the biosynthesis of anthracyclines, which has allowed generation of novel compound libraries by metabolic engineering and combinatorial biosynthesis. Coupled to the continued discovery of new congeners from rare Actinobacteria, a better understanding of the biology of Streptomyces and improved production methodologies, the stage is set for the development of novel anthracyclines that can finally surpass doxorubicin at the forefront of cancer chemotherapy.
Covering: January 1995 to June 2021 Anthracyclines are glycosylated microbial natural products that harbour potent antiproliferative activities. Doxorubicin has been widely used as an anticancer agent in the clinic for several decades, but its use is restricted due to severe side-effects such as cardiotoxicity. Recent studies into the mode-of-action of anthracyclines have revealed that effective cardiotoxicity-free anthracyclines can be generated by focusing on histone eviction activity, instead of canonical topoisomerase II poisoning leading to double strand breaks in DNA. These developments have coincided with an increased understanding of the biosynthesis of anthracyclines, which has allowed generation of novel compound libraries by metabolic engineering and combinatorial biosynthesis. Coupled to the continued discovery of new congeners from rare Actinobacteria, a better understanding of the biology of Streptomyces and improved production methodologies, the stage is set for the development of novel anthracyclines that can finally surpass doxorubicin at the forefront of cancer chemotherapy.