A1 Refereed original research article in a scientific journal
The Rieske Oxygenase SnoT Catalyzes 2''-Hydroxylation of L-Rhodosamine in Nogalamycin Biosynthesis
Authors: Nji Wandi Benjamin, Siitonen Vilja, Palmu Kaisa, Metsä-Ketelä Mikko
Publisher: Wiley - V C H Verlag GmbH & Co. KGaA
Publication year: 2020
Journal: ChemBioChem
Volume: 21
Issue: 21
First page : 3062
Last page: 3066
Number of pages: 6
ISSN: 1439-4227
eISSN: 1439-7633
DOI: https://doi.org/10.1002/cbic.202000229(external)
Web address : https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202000229(external)
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/47698497(external)
Nogalamycin is an anthracycline anti-cancer agent that intercalates into the DNA double helix. The binding is facilitated by two carbohydrate units, L-nogalose and L-nogalamine, that interact with the minor and major grooves of DNA, respectively. However, recent investigations have shown that nogalamycin biosynthesis proceeds through the attachment of l-rhodosamine (2′′-deoxy-4′′-epi-L-nogalamine) to the aglycone. Herein, we demonstrate that the Rieske enzyme SnoT catalyzes 2′′-hydroxylation of L-rhodosamine as an initial post-glycosylation step. Furthermore, we establish that the reaction order continues with 2–5′′ carbocyclization and 4′′ epimerization by the non-heme iron and 2-oxoglutarate-dependent enzymes SnoK and SnoN, respectively. These late-stage tailoring steps are important for the bioactivity of nogalamycin due to involvement of the 2′′- and 4′′-hydroxy groups of ᴸ-nogalamine in hydrogen bonding interactions with DNA.
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