Vertaisarvioitu katsausartikkeli tieteellisessä aikakauslehdessä (A2)
Anthracyclines: biosynthesis, engineering and clinical applications
Julkaisun tekijät: Hulst Mandy B., Grocholski Thadee, Neefjes Jacques J.C., van Wezel Gilles P., Metsä-Ketelä Mikko
Kustantaja: Royal Society of Chemistry
Julkaisuvuosi: 2022
Journal: Natural Product Reports
Tietokannassa oleva lehden nimi: NATURAL PRODUCT REPORTS
Lehden akronyymi: NAT PROD REP
Volyymi: 39
Julkaisunumero: 4
Aloitussivu: 814
Lopetussivun numero: 841
Sivujen määrä: 28
ISSN: 0265-0568
eISSN: 1460-4752
DOI: http://dx.doi.org/10.1039/d1np00059d
Tiivistelmä
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.